Grupos Investigadores

Líneas de Investigación

  • Nutrición: FODMAPS. Medidas higiénico-dietéticas (alimentación y actividad física)
  • Estudio del impacto de la cirugía bariátrica/metabólica: Efectos clínicos sobre las comorbilidades. Mecanismos de acción subyacentes
  • Adipobiología y desarrollo de comorbilidades asociadas a la obesidad: -Relevancia clínica de la composición corporal. -Bases moleculares del exceso de adiposidad/lipotoxicidad

Palabras Clave

  • Sobrepeso
  • Obesidad
  • Matriz extracelular
  • Hipertensión
  • Fibrosis
  • Esteatosis
  • Esteatohepatitis
  • Enfermedades cardiovasculares
  • Diabetes
  • Composición corporal
  • Comorbilidades
  • Cirugía bariátrica/metabólica
  • Apnea obstructiva del sueño
  • Adiposidad
  • Adipoquinas

Publicaciones Científicas desde 2018

  • Autores: Catalán Goñi, Victoria; Avilés Olmos, Iciar; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.14 N° 8 2022 págs. 1597
    Resumen
    The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent the main contributors to the obesity problem, they are not able to fully explain all cases and current trends. In this context, a body of knowledge related to exposure to as yet underappreciated obesogenic factors, which can be referred to as the "exposome", merits detailed analysis. Contrarily to the genome, the "exposome" is subject to a great dynamism and variability, which unfolds throughout the individual's lifetime. The development of precise ways of capturing the full exposure spectrum of a person is extraordinarily demanding. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to this global epidemic. This narrative review reports the available evidence on as yet underappreciated drivers of the obesity epidemic. Broadly based interventions are needed to better identify these drivers at the same time as stimulating reflection on the potential relevance of the "exposome" in the development and perpetuation of the obesity epidemic.
  • Autores: Botana, M.; Escalada San Martín, Francisco Javier; Merchante, A.; et al.
    Revista: DIABETES THERAPY
    ISSN 1869-6953 Vol.13 N° Supl. 1 2022 págs. 5 - 17
    Resumen
    Heart failure (HF) and chronic kidney disease (CKD) are the most frequent first cardiorenal conditions in patients with type 2 diabetes (T2D), which can be exacerbated by other comorbidities, such as hypertension, dyslipidemia, and obesity. To improve their clinical outcomes, patients with T2D need to achieve and maintain glycemic targets, as well as prevent cardiorenal disease onset and progression. Several clinical trials evaluating the sodium-glucose cotransporter type 2 inhibitors (SGLT2i) dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin have shown consistent risk reduction in major adverse cardiovascular events and/or hospitalization for HF, together with lower risk of kidney disease progression. The benefits associated with SGLT2i in T2D are distinct from other antihyperglycemic drugs since they have been proposed to exert pleiotropic metabolic and direct effects on the kidney and the heart. In this review, we summarize and discuss the evidence regarding the mechanisms of action, the efficacy and safety profiles, and the clinical guidelines on the use of the therapeutic class of SGLT2i, highlighting their role in cardiorenal prevention beyond glycemic control.
  • Autores: Aliseda Jover, Daniel (Autor de correspondencia); Álvarez-Cienfuegos Suárez, Francisco Javier; Valentí Azcarate, Víctor; et al.
    Revista: ANZ JOURNAL OF SURGERY
    ISSN 1445-1433 Vol.92 N° 3 2022 págs. 620 - 620
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.114 N° 2 2022 págs. 73 - 75
  • Autores: Escalada San Martín, Francisco Javier
    Revista: DIABETES THERAPY
    ISSN 1869-6953 Vol.13 N° Supl. 1 2022 págs. 1 - 3
  • Autores: Gómez Ambrosi, Javier
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.14 N° 3 2022 págs. 421
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia); Catalán Goñi, Victoria; Fruhbeck Martínez, Gema
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° 5 2022 págs. e13723
  • Autores: Baixauli Fons, Jorge; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Martínez Regueira, Fernando; et al.
    Revista: SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
    ISSN 1530-4515 Vol.32 N° 1 2022 págs. 28 - 34
    Resumen
    Background: Laparoscopic resection is the treatment of choice for colorectal cancer. Rates of conversion to open surgery range between 7% and 30% and controversy exists as to the effect of this on oncologic outcomes. The objective of this study was to analyze what factors are predictive of conversion and what effect they have on oncologic outcomes. Methods: From a prospective database of patients undergoing laparoscopic surgery between 2000 and 2018 a univariate and multivariate analyses were made of demographic, pathologic, and surgical variables together with complementary treatments comparing purely laparoscopic resection with conversions to open surgery. Overall and disease-free survival were compared using the Kaplan-Meier method. Results: Of a total of 829 patients, 43 (5.18%) converted to open surgery. In the univariate analysis, 12 variables were significantly associated with conversion, of which left-sided resection [odds ratio (OR): 2.908; P=0.02], resection of the rectum (OR: 4.749, P=0.014), and local invasion of the tumor (OR: 6.905, P<0.01) were independently predictive factors in the multiple logistic regression. Female sex was associated with fewer conversions (OR: 0.375, P=0.012). The incidence and pattern of relapses were similar in both groups and there were no significant differences between overall and disease-free survival. Conclusions: Left-sided resections, resections of the rectum and tumor invasion of neighboring structures are associated with higher rates of conversion. Female sex is associated with fewer conversions. Conversion to open surgery does not compromise oncologic outcomes at 5 and 10 years.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN 1664-3224 Vol.13 2022 págs. 832185
    Resumen
    Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue (AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36 gamma, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36 gamma was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of IL36G and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36 gamma was determined in vitro in human adipocytes and macrophages. We found, for the first time, that the increased (P<0.05) circulating levels of IL-36 gamma in patients with obesity decreased (P<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of IL36G were upregulated in the visceral AT (P<0.05) and in the peripheral blood mononuclear cells (P<0.01) from patients with obesity. We also demonstrated increased (P<0.05) expression levels of Il36g in the epididymal AT from diet-induced obese mice. IL36G was significantly enhanced (P<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36 gamma for 24 h strongly induced (P<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (P<0.01) the release of IL-36 gamma and the expression (P<0.05) of cathepsin G (CTSG) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36 gamma in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Becerril Mañas, Sara; et al.
    Revista: ACTA BIOMATERIALIA
    ISSN 1742-7061 Vol.141 2022 págs. 264 - 279
    Resumen
    Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improvements. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with enhanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E , UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better characterization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.
  • Autores: Baenas, I.; Etxandi, M.; Munguia, L.; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.14 N° 1 2022 págs. 100
    Resumen
    Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
  • Autores: Ripolles-Melchor, J.; Sánchez-Santos, R.; Abad-Motos, A. (Autor de correspondencia); et al.
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.32 N° 4 2022 págs. 1289 - 1299
    Resumen
    Purpose: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. Materials and methods: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions.
  • Autores: Di Ciaula, A.; Bonfrate, L.; Krawczyk, M.; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN 1422-0067 Vol.23 N° 5 2022 págs. 2636
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
  • Autores: León-Jiménez, D. (Autor de correspondencia); Miramontes-González, J. P. (Autor de correspondencia); Márquez-López, L.; et al.
    Revista: DIABETIC MEDICINE
    ISSN 0742-3071 Vol.39 N° 2 2022 págs. e14679
    Resumen
    Background Diabetic kidney disease is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. ESKD has a high prevalence in patients with diabetes mellitus (DM). CKD increases the chances of hypoglycaemia by different mechanisms, causes insulin resistance and a decrease in insulin metabolism. Both the "Kidney Disease: Improving Global Outcomes" (KDIGO) and "American Diabetes Association" (ADA) guidelines recommend the use of insulin as part of treatment, but the type of basal insulin is not specified. Methods We reviewed the literature to determine whether first- and second-generation basal insulins are effective and safe in CKD patients. We reviewed specific pivotal studies conducted by pharmaceutical laboratories, as well as independent studies. Conclusions Basal insulins are safe and effective in patients with CKD and diabetes mellitus but we do not have specific studies. Given that CKD is one of the main complications of type 2 DM, and insulin specific treatment in the final stages, the absence of studies is striking. Real-life data are also important since trials such as pivotal studies do not fully represent actual patients. Treatment should be individualized until we have specific trials in this type of population.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Ramírez, B.; et al.
    Revista: JOURNAL OF INFLAMMATION RESEARCH
    ISSN 1178-7031 Vol.15 2022 págs. 1331 - 1345
    Resumen
    Background: Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. Methods: Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). Results: Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OBIGT&T2D group (NW 440 +/- 316, OB-NG 899 +/- 562, OB-IGT&T2D 1265 +/- 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 +/- 1009 to 660 +/- 538 pg/ mL (P<0.001). Conclusion: Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.
  • Autores: Zugasti-Murillo, A.; Tejera-Pérez, C. (Autor de correspondencia); Rubio-Herrera, M. A.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.69 N° 3 2022 págs. 219 - 226
    Resumen
    Introducción La enfermedad COVID-19 se ha convertido en una prioridad para nuestro sistema sanitario. Los MIR de Endocrinología y Nutrición (MIR-EyN) se han integrado en los equipos COVID-19. Se ha diseñado este estudio con el objetivo de analizar el impacto a nivel formativo, laboral y en la salud de los MIR-EyN. Material y métodos Estudio observacional transversal tipo encuesta vía web, dirigida a los MIR-EyN socios de la SEEN, realizado en noviembre de 2020. Se han analizado: variables demográficas, tamaño del hospital de formación en número de camas, alteración de las rotaciones, integración en equipos COVID-19, participación en teleconsulta, actividad científica e impacto sobre la salud física y emocional. Resultados Se han obtenido 87 respuestas (27% de los MIR-EyN); 67,8% mujeres, edad media 28,1 ± 1,8 años, 60% MIR-EyN 4.o año. El 84% ha participado en equipos COVID-19 y el 93% en las consultas telemáticas de su servicio. La mayoría ha visto interrumpidas sus rotaciones. El 97,7% ha participado en reuniones científicas o congresos virtuales y un tercio de ellos ha colaborado en trabajos científicos sobre la COVID-19 en relación con la Endocrinología y Nutrición. La pandemia ha afectado a su estado de ánimo mucho o bastante (75,8%) y opinan que ha impactado de forma negativa a su formación (73,8%). Conclusiones La pandemia por SARS-CoV-2 ha comprometido la formación, la actividad laboral y la salud de los MIR-EyN. Se han integrado tanto en equipos COVID-19 como en la actividad reestructurada de sus servicios. Sin embargo, han conseguido mantener la formación en formato virtual y participado en trabajos científicos.
  • Autores: Perdomo Zelaya, Carolina María (Autor de correspondencia); Ezponda Casajús, Ana; Núñez Córdoba, Jorge María; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.12 N° 1 2022 págs. 6564
    Resumen
    Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.
  • Autores: Fernández González, Secundino (Autor de correspondencia); Ferrán de la Cierva, Sol; Garaycochea Mendoza del Solar, Octavio
    Revista: CLINICAL CASE REPORTS
    ISSN 2050-0904 Vol.10 N° 3 2022 págs. e05476
    Resumen
    We report the case of a 48-year-old woman, a teacher, with recurrent severe dysphonia and multiple and different lesions at the same time in her vocal folds. The evolution of the lesions and the possible mechanism by which they have been associated in the same patient are commented.
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bischoff, S. C.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.15 N° 3 2022 págs. 321 - 335
    Resumen
    Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases), and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of an universally established SO Definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a Definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into Stage I in the absence of clinical complications, or Stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO Definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition.
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bischoff, S. C.; et al.
    Revista: CLINICAL NUTRITION
    ISSN 0261-5614 Vol.41 N° 4 2022 págs. 990 - 1000
    Resumen
    Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases), and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of an universally established SO Definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a Definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into Stage I in the absence of clinical complications, or Stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO Definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Becerril Mañas, Sara; Martín Rodríguez, Marina; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN 0026-0495 Vol.128 2022 págs. 155119
    Resumen
    Background: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were determined in patients with severe obesity (n = 41) as well as in rats with diet-induced obesity (n = 48), monogenic obesity (Zucker fa/fa) (n = 18) or in a food choice paradigm (normal diet vs high-fat diet) (n = 16) submitted to sleeve gastrectomy. Lingual distribution and expression of guanylins (GUCA2A and GUCA2B) and their receptor GUCY2C as well as the fatty acid receptor CD36 were evaluated in the preclinical models. Results: Circulating concentrations of GUCA2A and GUCA2B were increased after sleeve gastrectomy in patients with severe obesity as well as in rats with diet-induced and monogenic (fa/fa) obesity. Interestingly, the lower dietary fat preference observed in obese rats under the food choice paradigm as well as in patients with obesity after sleeve gastrectomy were negatively associated with post-surgical GUCA2B levels. Moreover, sleeve gastrectomy upregulated the low expression of GUCA2A and GUCA2B in taste bud cells of tongues from rats with diet induced and monogenic (fa/fa) obesity in parallel to a downregulation of the lingual lipid sensor CD36. Conclusions: The increased circulating and lingual GUCA2B after sleeve gastrectomy suggest an association between the uroguanylin-GUCY2C endocrine axis and food preference through the regulation of gustatory responses. (c) 2022 Elsevier Inc. All rights reserved.
  • Autores: Yárnoz-Esquiroz, P.; Olazarán, L.; Aguas-Ayesa, M.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° 7 2022 págs. e13811
    Resumen
    Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of "obesities" makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed "obesities" are required.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Ramírez, B.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Bonfrate, L.; Wang, D. Q. H.; Fruhbeck Martínez, Gema; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Gómez Ambrosi, Javier
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Valentí Azcarate, Víctor; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Fruhbeck Martínez, Gema; Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Landecho Acha, Manuel Fortún (Autor de correspondencia); Marin Oto, Marta; Recalde Zamacona, Borja; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN 0953-6205 Vol.91 2021 págs. 3 - 9
    Resumen
    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.
  • Autores: Tuero, C. (Autor de correspondencia); Docio, G.; Valentí Azcarate, Víctor; et al.
    Revista: WORLD JOURNAL OF LAPAROSCOPIC SURGERY
    ISSN 0974-5092 Vol.14 N° 2 2021 págs. 141 - 143
    Resumen
    Aim and objective: The aim and objective of this article was to focus on long-term complications after bariatric surgery, which are usually managed by general surgeons in the emergency department. Background: Roux-en-Y gastric bypass (RYGBP) is one of the most commonly performed bariatric techniques in the world. Gastric remnant complications after this procedure are infrequent and poorly known. Furthermore, the diagnosis of this pathology may be challenging. Case description: We present the case of a 54-year-old woman with intense epigastric pain and history of uncomplicated laparoscopic RYGBP 18 years ago. After clinical, laboratory, and radiological examinations, the patient was diagnosed with a gastric remnant perforation. Laparoscopic surgery was performed, and the perforation was successfully repaired with primary suture and omental patch. Conclusion: Gastric remnant perforation after bariatric surgery is not frequent and usually appears several years after the procedure. This type of pathology is presented without specific clinical manifestations and with few analytical alterations. Complementary radiological studies, such as computed tomography (CT) scan, should be performed. However, pneumoperitoneum and extravasation of oral contrast are usually absent. Depending on the size of the defect, primary suture or gastric remnant resection may be performed. Nevertheless, surgical treatment should not be delayed. Clinical significance: Long-term complications after bariatric surgery are in many circumstances managed by general practitioner surgeons. The low incidence and scarce manifestations make the diagnosis of this pathology challenging. Furthermore, bariatric surgery is progressively increasing its presence all over the world. Complications after this procedure must be known and kept in mind because an early diagnosis is crucial to give a proper treatment and reduce morbidity and mortality.
  • Autores: Escalada San Martín, Francisco Javier
    Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO
    ISSN 2628-491X Vol.2 N° 3 2021 págs. 309 - 312
  • Autores: Fondevila, M. F.; Mercado-Gómez, M.; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN 0168-8278 Vol.74 N° 2 2021 págs. 469 - 471
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.113 N° 7 2021 págs. 554 - 554
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: JAMA SURGERY
    ISSN 2168-6254 Vol.156 N° 12 2021 págs. 1183 - 1183
  • Autores: Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.51 N° 9 2021 págs. e13586
  • Autores: Landecho Acha, Manuel Fortún; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: OBESITY
    ISSN 1930-7381 Vol.29 N° 1 2021 págs. 19
    Resumen
    As of October 2020, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS¿CoV¿2), responsible for Coronavirus Disease 2019 (COVID¿19), has infected over 33million individuals and killed over one million people worldwide. (https://coronavirus.jhu.edu/map.html accessed October 1 2020) Obesity and its complications are linked to severe forms of COVID¿19, favouring an increased hospitalization and mortality rate. Despite being the gold¿standard for the treatment of selected individuals with severe obesity, there is scarce information on whether or not bariatric surgery modifies the prognosis of people living with obesity in the current COVID¿19 pandemic. Bel Lassen and colleagues have carried out the first study with a high number of patients in their sample, bringing light into this area of uncertainty. The authors provide evidence of the importance of diabetes itself as a risk factor for severe COVID¿19.
  • Autores: Dicker, D.; Golan, R. (Autor de correspondencia); Baker, J. L.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.14 N° 3 2021 págs. 334 - 335
  • Autores: Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Alcalde Navarrete, Juan Manuel; Fernández González, Secundino
    Revista: JOURNAL OF VOICE
    ISSN 0892-1997 Vol.35 N° 6 2021 págs. 930
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Pérez, A.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 2 2021 págs. 79 - 81
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Valentí Azcarate, Víctor; et al.
    Revista: CELLULAR AND MOLECULAR IMMUNOLOGY
    ISSN 1672-7681 Vol.18 N° 10 2021 págs. 2457 - 2459
  • Autores: Escalada San Martín, Francisco Javier
    Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO
    ISSN 2628-491X Vol.2 N° 3 2021 págs. 305 - 308
  • Autores: Breton, I. (Autor de correspondencia); de Hollanda, A.; Vilarrasa, N.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 8 2021 págs. 573 - 576
  • Autores: Becerril Mañas, Sara; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET
    ISSN 0140-6736 Vol.397 N° 10286 2021 págs. 1687 - 1689
  • Autores: Reyes-García, R. (Autor de correspondencia); Mezquita-Raya, P.; Moreno-Pérez, O.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 4 2021 págs. 270 - 276
    Resumen
    Objective: To provide practical recommendations for the evaluation and management of hypo-glycemia in patients with diabetes mellitus. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endo-crinology and Nutrition (SEEN). Methods: The recommendations were made based on the Grading of Recommendations, Assess-ment, Development and Evaluation (GRADE) system to establish both the strength of the recommendations and the level of evidence. A systematic search was made in MEDLINE (Pub -Med) for the available evidence on each subject, and articles written in English and Spanish with an inclusion date up to 28 February 2020 were reviewed. This executive summary takes account of the evidence incorporated since 2013. Conclusions: The document establishes practical evidence-based recommendations regarding the evaluation and management of hypoglycemia in patients with diabetes mellitus.
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia); Puig-Domingo, M.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 7 2021 págs. 447 - 449
  • Autores: Currás Freixes, María (Autor de correspondencia); Salvador Rodríguez, Javier
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN 0014-2565 Vol.221 N° 1 2021 págs. 30 - 32
  • Autores: Dicker, D. (Autor de correspondencia); Alfadda, A. A.; Coutinho, W.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN 0953-6205 Vol.91 2021 págs. 10 - 16
    Resumen
    Background: People with obesity (PwO) often struggle to achieve and maintain weight loss. This can perpetuate and/or be influenced by feelings of low motivation. This analysis from ACTION-IO data identified factors associated with PwO motivation to lose weight. Methods: PwO completed an online survey in 11 countries. Exploratory multinomial logistic regression analyses identified independent variables associated with self-report of feeling motivated versus not motivated to lose weight. Results: Data from 10,854 PwO were included (5,369 motivated; 3,312 neutral; 2,173 not motivated). Variables associated with feeling motivated versus not motivated included (odds ratio [95% confidence interval]): acknowledgement of healthcare professional (HCP) responsibility to contribute to weight loss (2.32 [1.86-2.88]), comfort in talking to their HCP about weight (1.46 [1.24-1.72), agreement that it is easy to lose weight (1.73 [1.30-2.31]), and a goal of reducing risks from excess weight (1.45 [1.22-1.73]). Conversely, if PwO considered obesity less important than other diseases they were less likely to report feeling motivated (0.49 [0.41-0.58]). PwO who reported being motivated to lose weight were more likely to exercise >= 5 times a week versus <1 time a week (2.77 [2.09-3.68]) than those who reported they were not motivated. Conclusions: Positive interactions with HCPs, self-efficacy, setting goals and knowledge of the importance of weight management, in addition to regular exercising, may increase PwO motivation for weight loss. Appropriate HCP support may help PwO who are ready to engage in weight management. Clinical trial registration: : NCT03584191.
  • Autores: Zapata Cardenas, Juana Karina; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.13 N° 4 2021 págs. 1216
    Resumen
    In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8-10 (n = 38), 11-13 (n = 50), and 14-17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8-10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8-10 year-olds.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: CELLULAR AND MOLECULAR IMMUNOLOGY
    ISSN 1672-7681 Vol.18 N° 4 2021 págs. 1045 - 1057
    Resumen
    The NLRP3-IL-1 beta pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix (ECM) remodeling. Samples obtained from 98 subjects were used in a case-control study. The expression of different components of the inflammasome as well as their main effectors and inflammation- and ECM remodeling-related genes were analyzed. The impact of blocking NLRP3 using siRNA in lipopolysaccharide (LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated. We demonstrated that obesity (P < 0.01), obesity-associated T2D (P < 0.01) and NAFLD (P < 0.05) increased the expression of different components of the inflammasome as well as the expression and release of IL-1 beta and IL-18 in AT. We also found that obese patients with T2D exhibited increased (P < 0.05) hepatic gene expression levels of NLRP3, IL1B and IL18. We showed that NLRP3, but not NLRP1, is regulated by inflammation and hypoxia in visceral adipocytes. We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked (P < 0.01) LPS-induced inflammation by downregulating the mRNA levels of CCL2, IL1B, IL6, IL8, S100A8, S100A9, TLR4 and TNF as well as inhibiting (P < 0.01) the secretion of IL1-beta into the culture medium. Furthermore, blocking NLRP3 attenuated (P < 0.01) the LPS-induced expression of important molecules involved in AT fibrosis (COL1A1, COL4A3, COL6A3 and MMP2). These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.
  • Autores: Santamaria Sandi, J. (Autor de correspondencia); Navarro González, E.; Herrero Ruiz, A.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 8 2021 págs. 577 - 588
    Resumen
    Endocrinology and Nutrition is a medical specialty covering the study and treatment of diseases of the endocrine system, metabolism and those derived from the nutritional process, including knowledge of diagnostic techniques and dietary and therapeutic measures. In order to develop these activities and plan the management of resources allocated for this purpose, the so-called Portfolio of Services of the specialty has to be defined. A Portfolio of Services is defined as the set of techniques, technologies or procedures through which care services are provided in a healthcare centre, department or institution. It is an essential tool for organization of a hospital Unit or Department by defining the roles and procedures of its healthcare professionals, and also for structuring the resources required to perform the activity. It also allows for defining how to use these resources and identifying the objectives to be achieved, improving the quality of clinical care. Finally, the definition and preparation of the portfolio of services makes it possible to have an inventory of the offer of healthcare services and to detect new healthcare needs. (c) 2021 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Testa, G.; Mora-Maltas, B.; Camacho-Barcia, L.; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.13 N° 12 2021
    Resumen
    Impulsive and compulsive behaviors have both been observed in individuals with obesity. The co-occurrence of obesity and type 2 diabetes (T2D) is more strongly associated with impulsivity, although there are no conclusive results yet. A multidimensional assessment of impulsivity and compulsivity was conducted in individuals with obesity in the absence or presence of T2D, compared with healthy, normal-weight individuals, with highly impulsive patients (gambling disorders), and with highly compulsive patients (anorexia nervosa). Decision making and novelty seeking were used to measure impulsivity, and cognitive flexibility and harm avoidance were used for compulsivity. For impulsivity, patients with obesity and T2D showed poorer decision-making ability compared with healthy individuals. For compulsivity, individuals with only obesity presented less cognitive flexibility and high harm avoidance; these dimensions were not associated with obesity with T2D. This study contributes to the knowledge of the mechanisms associated with diabetes and its association with impulsive-compulsive behaviors, confirming the hypothesis that patients with obesity and T2D would be characterized by higher levels of impulsivity.
  • Autores: Díez Goñi, María de las Nieves (Autor de correspondencia); Pacheco, S.; Llorente Ortega, Marcos; et al.
    Revista: OTOLARYNGOLOGY-HEAD AND NECK SURGERY
    ISSN 0194-5998 Vol.164 N° 2 2021 págs. 339 - 345
    Resumen
    Objective To validate a simulator for upper airway examination, fitted with sensors, for use as an academic tool for learning how to conduct examination of the upper airway and for evaluation of that learning. Study Design Validation study. Setting Undergraduate medical education. Subjects and Methods A group of 18 fifth-year medical students and another of 6 otorhinolaryngology specialists conducted 6 examinations each with the simulator. To investigate concurrent validity, we calculated the correlation between damage scores provided by the simulator and damage assessment by a specialist. To evaluate construct validity, we compared both groups with regard to damage scores, technical procedure, and time spent. To examine content and face validity, we used questionnaires based on a 5-point Likert scale. Results For concurrent validity, the correlation between the simulator's damage scores and the specialist's damage assessment was high: Spearman's rho was 0.828 (P< .001). For construct validity, the group of students differed from the group of specialists in damage scores (P= .027) and in technical procedures (P< .001) but not in time spent. For content validity, all questionnaire statements were scored highly, and both groups had similar average scores. For face validity, the group of specialists considered the simulator to be realistic, and all statements on the questionnaire were rated with at least 4/5. Conclusion Concurrent, construct, content, and face validity have been demonstrated for a sensor-fitted simulator for upper airway examination, which is therefore accurate enough to be used as an academic tool for learning and evaluation of learning.
  • Autores: Llavero Valero, María; Escalada San Martín, Francisco Javier; Martínez González, Miguel Ángel; et al.
    Revista: CLINICAL NUTRITION
    ISSN 0261-5614 Vol.40 N° 5 2021 págs. 2817 - 2824
    Resumen
    Background & aim: The association between ultra-processed foods (UPF) consumption and the risk of type 2 diabetes (T2D) has not been much explored. We aimed to evaluate the association between consumption of UPF and the incidence of T2D. Methods: We assessed 20,060 participants (61.5% women) from the SUN project (Seguimiento Universidad de Navarra) followed-up every two years (median follow-up 12 years). Food and drink consumption were evaluated through a validated 136-item food frequency questionnaire and grouped according to their degree of processing by the NOVA classification. Participants were categorized into tertiles of UPF consumption adjusted for total energy intake. We fitted Cox proportional hazard models with repeated dietary measurements at baseline and updating information on food consumption after 10 years of follow-up to minimise the potential effect of diet variation. Results: During 215,149 person-years of follow-up, 175 new-onset T2D cases were confirmed. Participants in the highest baseline tertile (high consumption) of UPF consumption had a higher risk of T2D as compared to those in the lowest tertile (multivariable adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.06 to 2.22) with a significant dose-response relationship (p for linear trend 1/4 0.024). The multivariable adjusted HR using repeated measurements of UPF intake was 1.65 (95% CI 1.14-2.38) when comparing extreme tertiles. Conclusions: In a highly-educated Mediterranean cohort with a low absolute risk, a higher intake of UPF was independently associated with a higher risk for T2D. These results provide more evidence to encourage the limitation of UPF consumption to reduce the population burden of T2D. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Autores: Granero Peiro, Lucia; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Baixauli Fons, Jorge; et al.
    Revista: SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
    ISSN 1530-4515 Vol.31 N° 5 2021 págs. 558 - 564
    Resumen
    Background: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer. Materials and Methods: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates. Results: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%. In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45). Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P = 0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P = 0.881). Conclusions: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.
  • Autores: Latorre, J.; Lluch, A.; Ortega, F. J.; et al.
    Revista: PHARMACOLOGICAL RESEARCH
    ISSN 1043-6618 Vol.166 2021 págs. 105486
    Resumen
    Chronic systemic low-level inflammation in metabolic disease is known to affect adipose tissue biology. Lysozyme (LYZ) is a major innate immune protein but its role in adipose tissue has not been investigated. Here, we aimed to investigate LYZ in human and rodents fat depots, and its possible role in obesity-associated adipose tissue dysfunction. LYZ mRNA and protein were identified to be highly expressed in adipose tissue from subjects with obesity and linked to systemic chronic-low grade inflammation, adipose tissue inflammation and metabolic disturbances, including hyperglycemia, dyslipidemia and decreased markers of adipose tissue adipogenesis. These findings were confirmed in experimental models after a high-fat diet in mice and rats and also in ob/ob mice. Importantly, specific inguinal and perigonadal white adipose tissue lysozyme (Lyz2) gene knockdown in high-fat diet-fed mice resulted in improved adipose tissue inflammation in parallel to reduced lysozyme activity. Of note, Lyz2 gene knockdown restored adipogenesis and reduced weight gain in this model. In conclusion, altogether these observations point to lysozyme as a new actor in obesity-associated adipose tissue dysfunction. The therapeutic targeting of lysozyme production might contribute to improve adipose tissue metabolic homeostasis.
  • Autores: Baptista Jardín, Peter Michael (Autor de correspondencia); Martinez Ruiz de Apodaca, P.; Carrasco, M.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.10 N° 9 2021 págs. 1883
    Resumen
    Study Objectives: Evaluating daytime neuromuscular electrical training (NMES) of tongue muscles in individuals with Primary Snoring and Mild Obstructive Sleep Apnea (OSA). Methods: A multicenter prospective study was undertaken in patients with primary snoring and mild sleep apnea where daytime NMES (eXciteOSA(R) Signifier Medical Technologies Ltd., London W6 0LG, UK) was used for 20 min once daily for 6 weeks. Change in percentage time spent snoring was analyzed using a two-night sleep study before and after therapy. Participants and their bed partners completed sleep quality questionnaires: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and the bed partners reported on the nighttime snoring using a Visual Analogue Scale (VAS). Results: Of 125 patients recruited, 115 patients completed the trial. Ninety percent of the study population had some reduction in objective snoring with the mean reduction in the study population of 41% (p < 0.001). Bed partner-reported snoring reduced significantly by 39% (p < 0.001). ESS and total PSQI scores reduced significantly (p < 0.001) as well as bed partner PSQI (p = 0.017). No serious adverse events were reported. Conclusions: Daytime NMES (eXciteOSA(R)) is demonstrated to be effective at reducing objective and subjective snoring. It is associated with effective improvement in patient and bed partner sleep quality and patient daytime somnolence. Both objective and subjective measures demonstrated a consistent ...
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Mentxaka, A.; Ahechu Garayoa, Patricia; et al.
    Revista: JOURNAL OF INFLAMMATION RESEARCH
    ISSN 1178-7031 Vol.14 2021 págs. 6431 - 6446
    Resumen
    Background: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC. Methods: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study. Results: CC (P<0.01) and obesity (P<0.01) were accompanied by increased mRNA levels of NLRP3, NLRP6, ASC, IL1B and NOD2 in VAT. Contrarily, patients with CC exhibited a downregulation of NLRP6 and IL18 in their colon. Additionally, we revealed that the decreased Nlrp1 (P<0.05), Nlrp3 (P<0.01) and Nlrp6 (P<0.01) mRNA levels in the colon from obese rats significantly increase (P<0.05) after caloric restriction. Adipocyteconditioned media obtained from subjects with obesity reduced (P<0.01) the mRNA of NLRP3 as well as molecules involved in maintaining the intestinal integrity (MUC2, CLDN1 and TJP1) and the anti-inflammatory factors FGF21, KLF4, and IL33 and in HT 29 cells. We also found that the knockdown of NLRP6 in HT-29 cells significantly upregulated (P<0.05) the mRNA of NLRP1 and NLRP3 and inhibited (P<0.05) the expression levels of MUC2. Finally, we showed that the incubation of HT-29 with Akkermansia muciniphila influence (P<0.05) the inflammasome expression profile as well as intestinal integrity-related genes and aberrant inflammation. Conclusions: These findings provide evidence that the downregulated levels of NLRP6 and IL18 in the colon from patients with CC may be responsible for a reduced intestinal-barrier integrity, triggering local inflammation, which in turn acts on the dysfunctional AT in obesity, increasing the expression of different inflammasome components and flaring up a vicious cycle of uncontrollable inflammatory cascades that favours a pro-tumorigenic microenvironment.
  • Autores: González-Rellán, M. J.; Fondevila, M. F.; Fernández, U.; et al.
    Revista: NATURE COMMUNICATIONS
    ISSN 2041-1723 Vol.12 N° 1 2021 págs. 5068
    Resumen
    p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.
  • Autores: Gómez de Segura, I.; Ahechu Garayoa, Patricia; Gómez Ambrosi, Javier; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN 1422-0067 Vol.22 N° 16 2021 págs. 8485
    Resumen
    Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 alpha 3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.
  • Autores: Francque, S. M. (Autor de correspondencia); Marchesini, G.; Kautz, A.; et al.
    Revista: JHEP REPORTS
    ISSN 2589-5559 Vol.3 N° 5 2021 págs. 100322
    Resumen
    This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.
  • Autores: Perdomo Zelaya, Carolina María; Gómez Ambrosi, Javier; Becerril Mañas, Sara; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN 1422-0067 Vol.22 N° 23 2021
    Resumen
    Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
  • Autores: Calvete, O. (Autor de correspondencia); Reyes, J.; Valdés-Socin, H.; et al.
    Revista: CELLS
    ISSN 2073-4409 Vol.10 N° 12 2021 págs. 3500
    Resumen
    Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid-base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid-base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.
  • Autores: Martín Rodríguez, Marina; Rodríguez Murueta-Goyena, Amaia; Gómez Ambrosi, Javier; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.13 N° 7 2021 págs. 2128
    Resumen
    Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.
  • Autores: Llorente Ortega, Marcos; Fernández González, Secundino (Autor de correspondencia)
    Revista: SIMULATION IN HEALTHCARE
    ISSN 1559-2332 Vol.16 N° 5 2021 págs. 367 - 371
    Resumen
    Introduction: The AirSim Multi (TruCorp) airway simulator is used to practice exploration of the upper respiratory tract with a flexible endoscope to assess the nasal cavities, their structures and spaces (inferior, middle, and superior turbinates and meati), and the nasopharynx. The passage of the flexible endoscope through the nose is usually the most annoying and painful maneuver to continue the exploration of the airway to the pharynx and larynx. For this reason, it is important to develop self-assessment training systems in safe environments that allow trainees to develop the necessary skills to carry out this type of assessment with the least inconvenience and the greatest security. Despite this simulator's accurate anatomical reproduction of the tract, its suitability as a tool for endoscope exploration learning is limited without a feedback system. Effective endoscopic exploration should not cause pain or lesions, not only for comfort and safety reasons, but also because only when discomfort is minimized is a complete and detailed exploration of the anatomical structures possible. The objective of the project was to provide a feedback system from the simulator to the trainee that would facilitate improvements in self-trained skills needed to perform an endoscopic exploration of the airways. Methods: A device based on the Hall-effect sensor was designed and placed outside the airway in the upper nasal turbinate. This device detects changes in the magnetic flux, indicating a displacement on the nasal turbinate due to endoscopic maneuvers that deform the inside of the simulator and would be expected to be harmful or painful in real life. Results: The improved AirSim provides audible and visual feedback during exploration to indicate a change on the nasal turbinate due to endoscopic contact with the turbinate surface that would be expected to be harmful or painful in real life. We expect this feature to facilitate self-learning with minimal professional supervision and reduce the overall training time required to successfully perform a complete exploration of the airway. Conclusions: The inclusion of sensors on a passive simulator is a cost-effective measure that may allow for better training experiences using AirSim Multi simulator from the TruCorp company. Our improved simulator turns endoscopic exploration into a self-assessed exercise suitable for all disciplines and level of learners.
  • Autores: Pomar, M. D. B. (Autor de correspondencia); García, N. V.; Herrera, M. A. R.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.68 N° 2 2021 págs. 130 - 136
    Resumen
    Obesity is one of the great challenges in healthcare nowadays with important impli-cations for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.seen.es, and that has been agreed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), together with the Nutrition Area (NutriSEEN) and the Working Group of Endocrinology, Nutrition and Physical Exercise (GENEFSEEN).
  • Autores: Alfadda, A. A. (Autor de correspondencia); Caterson, I. D.; Coutinho, W.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN 0953-6205 Vol.91 2021 págs. 17 - 25
    Resumen
    Background: The care of people with obesity is often suboptimal due to both physician and patient perceptions about obesity itself and clinical barriers. Using data from the ACTION-IO study, we aimed to identify factors that might improve the quality of obesity care through adoption of the 3D approach (Discussion, Diagnosis and Direction [follow-up]) by healthcare professionals (HCPs). Methods: An online survey was completed by HCPs in 11 countries. Exploratory beta regression analyses identified independent variables associated with each component of the 3D approach. Results: Data from 2,331 HCPs were included in the statistical models. HCPs were significantly more likely to initiate weight discussions and inform patients of obesity diagnoses, respectively, if (odds ratio [95% confidence interval]): they recorded an obesity diagnosis in their patient's medical notes (1.59, [1.43-1.76] and 2.16 [1.94-2.40], respectively); and they were comfortable discussing weight with their patients (1.53 [1.39-1.69] and 1.15 [1.04-1.27]). HCPs who reported feeling motivated to help their patients lose weight were also more likely to initiate discussions (1.36 [1.21-1.53]) and schedule follow-up appointments (1.21 [1.06-1.38]). By contrast, HCPs who lacked advanced formal training in obesity management were less likely to inform patients of obesity diagnoses (0.83 [0.74-0.92]) or schedule follow-up appointments (0.69 [0.62-0.78]). Conclusion: Specific actions that could improve obesity care through the 3D approach include: encouraging HCPs to record an obesity diagnosis; providing tools to help HCPs feel more comfortable initiating weight discussions; and provision of training in obesity management. Clinical trial registration: NCT03584191.
  • Autores: Chiva San Román, Santiago; Polo-Gay, R.; Muñoz Bastidas, Carmina Alejandra; et al.
    Revista: EUROPEAN UROLOGY
    ISSN 0302-2838 Vol.79 N° Supl. 1 2021 págs. S1355
  • Autores: Gonzalez Rellan, M. J.; Fernández Fondevila, M.; Fernández Paz, U.; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN 0168-8278 Vol.75 N° Supl. 2 2021 págs. S249 - S250
  • Autores: Fruhbeck Martínez, Gema
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.51 N° Supl. 1 2021 págs. 71
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bauer, J. M. ; et al.
    Revista: CLINICAL NUTRITION
    ISSN 0261-5614 Vol.39 N° 8 2020 págs. 2368 - 2388
    Resumen
    Background: Sarcopenic obesity is a clinical and functional condition characterized by the coexistence of excess fat mass and sarcopenia. Currently, different definitions of sarcopenic obesity exist and its diagnostic criteria and cut-offs are not universally established. Therefore, the prevalence and sensitivity of this condition for any disease risk prediction is affected significantly. Aim: This work was conducted under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). An international expert panel performed a systematic review as an initial step to analyze and summarize the available scientific literature on the definitions and the diagnostic criteria for sarcopenic obesity proposed and/or applied in human studies to date. Methods: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in April 2018 in three databases (PubMed, Scopus, Web of Science). Human studies conducted in both sexes, irrespective of ethnicity, and published from 2007 to 2018 were included; cohorts of individuals with obesity and acute or chronic conditions and treatments reported to negatively influence skeletal muscle mass and function independently of obesity were excluded from final analyses. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) adapted for cross sectional studies. Results: The electronic search retrieved 2335 papers of which 75 met the eligibility criteria. A marked heterogeneity in definitions and approaches to diagnose sarcopenic obesity was observed. This was mainly due to differences in the definitions of obesity and sarcopenia, in the methodologies used to assess body composition and physical function, and in the reference values for the variables that have been used (different cut-offs, interquartile analysis, diverse statistical stratification methods). This variability may be attributable, at least in part, to the availability of the methodologies in the different settings, to the variability in specialties and backgrounds of the researcher, and to the different settings (general population, clinical settings, etc.) where studies were performed. Conclusion: The results of the current work support the need for consensus proposals on: 1) definition of sarcopenic obesity; 2) diagnostic criteria both at the level of potential gold-standards and acceptable surrogates with wide clinical applicability, and with related cut-off values; 3) methodologies to be used in actions 1 and 2. First steps should be aimed at reaching consensus on plausible proposals that would need subsequent validation based on homogeneous studies and databases, possibly based on analyses of existing cohorts, to help define the prevalence of the condition, its clinical and functional relevance as well as most effective prevention and treatment strategies.
  • Autores: Rodríguez Murueta-Goyena, Amaia (Autor de correspondencia); Becerril Mañas, Sara; Hernandez-Pardos, A. W. ; et al.
    Revista: CURRENT OPINION IN PHARMACOLOGY
    ISSN 1471-4892 Vol.52 2020 págs. 1 - 8
    Resumen
    White (WAT) and brown (BAT) adipose tissue communicate with skeletal muscle and heart through the secretion of adipokines (adiponectin, leptin, omentin, osteopontin or cardiotrophin-1) and batokines (BMP8b, FGF-21, endothelin-1 or IL-6), respectively. Furthermore, several bioactive lipids termed lipokines [palmitoleate (C16:1n7) or 12,13-diHOME] and microRNAs capsuled in exosomes (miR-27a, miR122, miR-130b, miR-155, miR-200a or miR-320d) secreted from white and brown adipocytes also influence the skeletal and cardiac muscle function. The review focuses on the depot related differences in adipose tissue-derived signals (adipokines, batokines, lipokines and exosomal miRNAs) and their impact on skeletal muscle under physiological conditions as well as in obesity. The relevance of regular physical activity and exercise on fat depot-specific adaptations to improve metabolic health will also be addressed.
  • Autores: Valentí Azcarate, Víctor; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Becerril Mañas, Sara; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.112 N° 3 2020 págs. 229 - 233
    Resumen
    Bariatric-metabolic surgery is the safest, most effective and long-lasting treatment for obesity and its associated co-morbidities, whether they be metabolic (type 2 diabetes, hyperlipidemia non-alcoholic fatty liver disease) or cardiovascular (myocardial infarction, stroke). Due to the obesity pandemic, bariatric-metabolic surgery is the second most frequent intra-abdominal procedure and the gastroenterologist and the surgeon must be aware of the physiologic changes caused by the anatomic reconfiguration following surgery. Among the mechanisms of action, independent of the loss of weight and fat tissue, surgery leads to the release of gut hormones related to carbohydrate metabolism (the rapid and continuous release of insulin), appetite and degree of satiety (glucagon-like peptide 1, peptide Y-Y, grhelin). As a result, indications for surgery have been extended to earlier disease stages. Apart from the neurohormonal effects, changes in the metabolism of biliary acids and the microbiota have also been reported. The aim of this review is to describe the physiologic changes caused by bariatric-metabolic surgery.
  • Autores: Perdomo Zelaya, Carolina María; D'Ingianna , P.; Escalada San Martín, Francisco Javier; et al.
    Revista: POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE
    ISSN 0032-3772 Vol.130 N° 11 2020 págs. 975 - 985
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that encompasses various forms of liver damage not caused by chronic alcohol consumption. In the absence of other etiologies, it ranges from steatosis to nonalcoholic steatohepatitis and cirrhosis. The prevalence of NAFLD has considerably increased over the last years owing to the current lifestyle (unhealthy diet and sedentarism). Besides, it is associated with metabolic risk factors such as obesity, arterial hypertension, dyslipidemia, and type 2 diabetes. Given the poor prognosis of patients with advanced NAFLD, a practical therapeutic approach is necessary to halt its natural history. However, no licensed drugs have been approved for this purpose to date. Nowadays, we are in a race to find the first drug able to stop the incidence of NAFLD and reverse the disease in patients at more advanced stages. Meanwhile, the management of the NAFLD metabolic overload, including weight loss, cardiovascular protection, insulin sensitization, and lipid reduction, is the only strategy to improve hepatic and extrahepatic outcomes. In this review, we aimed to describe the management of the main metabolic disorders related to NAFLD, such as type 2 diabetes, arterial hypertension, and dyslipidemia.
  • Autores: van-Hulsteijn, L. T. (Autor de correspondencia); Pasquali, R.; Casanueva, F.; et al.
    Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
    ISSN 0804-4643 Vol.182 N° 1 2020 págs. 11 - 21
    Resumen
    Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.
  • Autores: Tuero Ojanguren, Carlota (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando; et al.
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.30 N° 7 2020 págs. 2763 - 2780
    Resumen
    Since the description of ghrelin in 1999, several studies have dug into the effects of this hormone and its relationship with bariatric surgery. While some aspects are still unresolved, a clear connection between ghrelin and the changes after metabolic surgery have been established. Besides weight loss, a significant amelioration in obesity-related comorbidities following surgery has also been reported. These changes in patients occur in the early postoperative period, before the weight loss appears, so that amelioration may be mainly due to hormonal changes. The purpose of this review is to go through the current body of knowledge of ghrelin's physiology, as well as to update and clarify the changes that take place in ghrelin concentrations following bariatric/metabolic surgery together with their potential consolidation to outcomes.
  • Autores: Silva Frojan, Camilo (Autor de correspondencia); García Goñi, Marta; Perdomo Zelaya, Carolina María
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.43 N° 3 2020 págs. 435 - 437
  • Autores: Fruhbeck Martínez, Gema; Baker, J. L.; Busetto, L.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.13 N° 2 2020 págs. 292 - 296
  • Autores: Alligier, M. ; Barres, R. ; Blaak, E. E.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.13 N° 1 2020 págs. 1 - 28
    Resumen
    Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.
  • Autores: Fruhbeck Martínez, Gema; Fernandez-Quintana, B. ; Paniagua, M.; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN 0026-0495 Vol.108 2020 págs. 154261
    Resumen
    Background: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. Methods: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. Results: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. Conclusions: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.
  • Autores: Hurtado Pardo, Luis; Álvarez-Cienfuegos Suárez, Francisco Javier; Antoñanzas Pérez, Javier; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.112 N° 2 2020 págs. 85 - 89
    Resumen
    Objective: the objective of the present study was to analyze the characteristics of resected incidental lesions of the pancreas. Material and methods: a retrospective study was performed of pancreatectomies due to incidentalomas between 1995 and 2018. Results: one hundred pancreatectomies were performed due to incidental lesions; 64 (64%) were solid and 36 (36%) were cystic lesions. The cytological analysis agreed with the diagnosis in 67/71 (88.7%) cases. Thirty-six tumors were cystic, 48 were neuroendocrine and 16 were adenocarcinomas. Disease-free survival for patients with cystic, neuroendocrine tumors and adenocarcinomas was 100%, 79% and 57.7% (p < 0.04). Conclusion: pancreatic incidentalomas have a heterogeneous phenotype and should be treated in experienced centers
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Bonnet, F.; Wu, J. ; et al.
    Revista: ADVANCES IN THERAPY
    ISSN 0741-238X Vol.37 N° 9 2020 págs. 3863 - 3877
    Resumen
    Introduction Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany. Methods This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naive patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice. Results Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (- 0.87% vs. - 0.93%;p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (- 1.29 vs. - 0.81 events during 6 months;p = 0.012). Mean insulin doses after titration were 0.43 +/- 0.36 and 0.40 +/- 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naive patients were broadly similar to those of switchers. Conclusions In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300.
  • Autores: Dicker, D. (Autor de correspondencia); Bettini, S.; Farpour-Lambert, N. ; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.13 N° 4 2020 págs. 430 - 438
    Resumen
    The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.
  • Autores: Ezquerro, S.; Becerril Mañas, Sara; Tuero, C.; et al.
    Revista: INTERNATIONAL JOURNAL OF OBESITY
    ISSN 0307-0565 Vol.44 N° 2 2020 págs. 475 - 487
    Resumen
    BACKGROUND/OBJECTIVES: Bariatric surgery improves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain elusive. We evaluated the potential role of ghrelin isoforms in the amelioration of hepatic inflammation after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). SUBJECTS/METHODS: Plasma ghrelin isoforms were measured in male Wistar rats (n¿=¿129) subjected to surgical (sham operation, sleeve gastrectomy, or RYGB) or dietary interventions [fed ad libitum a normal (ND) or a high-fat diet (HFD) or pair-fed diet]. The effect of acylated and desacyl ghrelin on markers of inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in primary rat hepatocytes under palmitate-induced lipotoxic conditions was assessed. RESULTS: Plasma desacyl ghrelin was decreased after sleeve gastrectomy and RYGB, whereas the acylated/desacyl ghrelin ratio was augmented. Both surgeries diminished obesity-associated hepatic steatosis, CD68+- and apoptotic cells, proinflammatory JNK activation, and Crp, Tnf, and Il6 transcripts. Moreover, a postsurgical amelioration in the mitochondrial DNA content, oxidative phosphorylation (OXPHOS) complexes I and II, and ER stress markers was observed. Specifically, following bariatric surgery GRP78, spliced XBP-1, ATF4, and CHOP levels were reduced, as were phosphorylated eIF2¿. Interestingly, acylated and desacyl ghrelin inhibited steatosis and inflammation of palmitate-treated hepatocytes in parallel to an upregulation of OXPHOS complexes II, III, and V, and a downregulation of ER stress transducers IRE1¿, PERK, ATF6, their downstream effectors, ATF4 and CHOP, as well as chaperone GRP78. CONCLUSIONS: Our data suggest that the increased relative acylated ghrelin levels after bariatric surgery might contribute to mitigate obesity-associated hepatic inflammation, mitochondrial dysfunction, and ER stress.
  • Autores: Weber, M. ; Mera, P.; Casas, J. ; et al.
    Revista: FASEB JOURNAL
    ISSN 0892-6638 Vol.34 N° 9 2020 págs. 11816 - 11837
    Resumen
    The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.
  • Autores: Vieira da Silva, I.; Cardoso, C.; Mendez-Gimenez, L.; et al.
    Revista: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
    ISSN 0003-9861 Vol.691 2020 págs. 108481
    Resumen
    Aquaporins (AQPs) facilitate water and glycerol movement across membranes. AQP7 is the main aquaglyceroporin in pancreatic beta-cells and was proposed to play a role in insulin exocytosis. Although AQP7-null mice display adult-onset obesity, impaired insulin secretion and insulin resistance, AQP7 loss-of-function homozygous mutations in humans do not correlate with obesity nor type-2 diabetes. In addition, AQP12 is upregulated in pancreatitis. However, the implication of this isoform in endocrine pancreas inflammation is still unclear. Here, we investigated AQP7 and AQP12 involvement in cellular and inflammatory processes using RIN-m5F beta cells, a model widely used for their high insulin secretion. AQP7 and AQP12 expression were directly associated with cell proliferation, adhesion and migration. While tumor necrosis factor-alpha (TNF alpha)-induced inflammation impaired AQP7 expression and drastically reduced insulin secretion, lipopolysaccharides (LPS) prompted AQP7 upregulation, and both TNF alpha and LPS upregulated AQP12. Importantly, cells overexpressing AQP12 are more resistant to inflammation, revealing lower levels of proinflammatory markers. Altogether, these data document AQP7 involvement in insulin secretion and AQP12 implication in inflammation, highlighting their fundamental role in pancreatic beta-cell function.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramirez, B.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.9 N° 4 2020 págs. 1069
    Resumen
    Compelling evidence suggests that dermatopontin (DPT) regulates collagen and fibronectin fibril formation, the induction of cell adhesion and the prompting of wound healing. We aimed to evaluate the role of DPT on obesity and its associated metabolic alterations as well as its impact in visceral adipose tissue (VAT) inflammation and extracellular matrix (ECM) remodelling. Samples obtained from 54 subjects were used in a case-control study. Circulating and VAT expression levels of DPT as well as key ECM remodelling- and inflammation-related genes were analysed. The effect of pro- and anti-inflammatory mediators on the transcript levels of DPT in visceral adipocytes was explored. The impact of DPT on ECM remodelling and inflammation pathways was also evaluated in cultured adipocytes. We show that obesity and obesity-associated type 2 diabetes (T2D) increased (p < 0.05) circulating levels of DPT. In this line, DPT mRNA in VAT was increased (p < 0.05) in obese patients with and without T2D. Gene expression levels of DPT were enhanced (p < 0.05) in human visceral adipocytes after the treatment with lipopolysaccharide, tumour growth factor (TGF)-beta and palmitic acid, whereas a downregulation (p < 0.05) was detected after the stimulation with interleukin (IL)-4 and IL-13, critical cytokines mediating anti-inflammatory pathways. Additionally, we revealed that DPT increased (p < 0.05) the expression of ECM- (COL6A3, ELN, MMP9, TNMD) and inflammation-related factors (IL6, IL8, TNF) in human visceral adipocytes. These findings provide, for the first time, evidence of a novel role of DPT in obesity and its associated comorbidities by influencing AT remodelling and inflammation.
  • Autores: Fernández González, Secundino; Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Martinez-Arellano, A.; et al.
    Revista: JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
    ISSN 1092-4388 Vol.63 N° 7 2020 págs. 2177 - 2184
    Resumen
    Objective: The aims of this study were to test the hypothesis that greater supraglottic compression (anteroposterior or lateral) correlates with higher subglottic pressure (SGP) and to develop a classification of muscle tension dysphonia (MTD), based on the degree of supraglottic compression during speech. Method: A prospective, cross-sectional study was conducted in a series of 37 consecutive patients diagnosed with MTD with an altered aerodynamic profile characterized by high SGP (more than 90 mmH(2)O). Supraglottic anteroposterior and lateral compression were categorized in three grades and assessed during the laryngoscopic examination. All patients completed the Spanish Voice Handicap Index (VHI) questionnaire and completed an acoustic and aerodynamic voice assessment. The relationship between compression grade and VHI with SGP was analyzed. Results: More than 90% of patients demonstrated some degree of anteroposterior compression, and 67% had some degree of lateral compression. The mean (SD) SGP was 111.03 (16.7) mmH(2)O, and the mean VHI was 27.86 (12.5). The degree of SGP was statistically different in the different grades of anteroposterior compression, and also anteroposterior compression correlated with an SGP (p < .05). The degree of lateral compression was not correlated with SGP. Neither the degree of anteroposterior or lateral compression nor the value of SGP was found to correlate with VHI. Conclusions: Because grade of anteroposterior compression correlates with SGP, these grades can be used for diagnosis and follow-up of MTD patients. To this end and on this basis, we propose a new classification for MTD. Unlike the established classification, our proposed one makes it possible to combine different laryngoscopic features, improving the description of the larynx during phonation.
  • Autores: Lujan Colas, Juan; Tuero Ojanguren, Carlota; Landecho Acha, Manuel Fortún; et al.
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.30 N° 11 2020 págs. 4293 - 4299
    Resumen
    Background Weight loss after bariatric surgery varies among patients. Patients who do not complete long-term follow-up are considered to loose less weight than those with regular follow-up visits. Objective To evaluate the influence of patients' follow-up compliance on long-term excess weight loss (%EWL) and total weight loss (%TWL) after bariatric surgery, comparing results between gastric bypass (GB) and sleeve gastrectomy (SG). Methods Patients with up to 5 years of follow-up data after bariatric surgery were included in this retrospective analysis. Patients were divided in 2 groups: those in group 1 who had attended every scheduled postoperative appointment and those in group 2 who had been lost to follow-up before 1 year and were later contacted by telephone. %EWL and %TWL were compared to determine the possible relationship between type of surgery and regularity of the follow-up. Results A total of 385 patients were included. A significant difference in EWL was observed at 5 years in the SG group (78% for group 1 versus 39% for group 2;p = 0.02) and GB group (75% for group 1 versus 62% for group 2;p = 0.01). No significant differences between surgeries were found when comparing long-term EWL in group 1 patients 77% for SG versus 75% for GB. For group 2 patients, GB achieved greater EWL than SG;p = 0.005. %TWL patients in group 2 showed significant differences in all periods of study (p < 0.05). Conclusion Bariatric surgery patients who attended all scheduled follow-up appointments experienced significantly greater long-term EWL and TWL than those who did not. GB has apparent increased benefits for weight loss in long-term follow-up when compared with SG for patients who did not attend long-term follow-up. Therefore, continued long-term follow-up of bariatric patients should be encouraged to increase postoperative weight loss results.
  • Autores: Fernandez-Aranda, F. (Autor de correspondencia); Munguia, L. ; Mestre-Bach, G. ; et al.
    Revista: EUROPEAN EATING DISORDERS REVIEW
    ISSN 1072-4133 Vol.28 N° 6 2020 págs. 871 - 883
    Resumen
    Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.
  • Autores: Sanchez, E.; Sanchez, M. ; Betriu, A.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.13 N° 1 2020 págs. 29 - 39
    Resumen
    Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53-63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clinica Universidad de Navarra - Body Adiposity Estimator [CUN-BAE], and Deurenberg's formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora's equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. -Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p <= 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p <= 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
  • Autores: GUARNIERI, Adriano (Autor de correspondencia); Carnero González, Elena María; Bleau, Anne Marie; et al.
    Revista: BMC OPHTHALMOLOGY
    ISSN 1471-2415 Vol.20 N° 1 2020 págs. 12
    Resumen
    BackgroundTear film stability is the key event in ocular surface diseases. The purpose of this study is to evaluate spatial and temporal progression of the tear film breakup using an automatic non-invasive device.MethodsNon-invasive tear breakup time (NITBUT) parameters, such as First NITBUT (F-NITBUT) and Average NITBUT (A-NITBUT), were evaluated in 132 glaucoma and 87 control eyes with the Keratograph 5M device. Further analysis of this data was used to determine size, location and progression of tear film breakup with automatically identified breakup areas (BUA). The progression from First BUA (F-BUA) to total BUA (T-BUA) was expressed as Dry Area Growth Rate (DAGR). Differences between both groups were analysed using Student t-test for parametric data and Mann-Whitney U test for non-parametric data. Pearson's correlation coefficient was used to assess the relationship between parametric variables and Spearman in the case of non-parametric variables.ResultsF-NITBUT was 11.437.83s in the control group and 8.17 +/- 5.73 in the glaucoma group (P=0.010). A-NITBUT was 14.04 +/- 7.21 and 11.82 +/- 6.09s in control and glaucoma groups, respectively (P=0.028). F-BUA was higher in the glaucoma group than in the control group (2.73 and 2.28; P=0.022) and was more frequently located at the centre of the cornea in the glaucoma group (P=0.039). T-BUA was also higher in the glaucoma group than in the control group (13.24 and 9.76%; P=0.012) and the DAGR was steeper in the glaucoma group than in the control group (34.38 degrees and 27.15 degrees; P=0.009).Conclusions Shorter NITBUT values and bigger, more central tear film breakup locations were observed in the glaucoma group than in the control group. The DAGR indicates that tear film rupture is bigger and increases faster in glaucomatous eyes than in normal eyes.
  • Autores: Castillo, A. M.; Valero-Rubira, I.; Burrell Bustos, María Ángela; et al.
    Revista: PLANTS
    ISSN 2223-7747 Vol.9 N° 11 2020 págs. 1442
    Resumen
    Microspores can be developmentally reprogrammed by the application of different stress treatments to initiate an embryogenic pathway leading to the production of doubled haploid (DH) plants. Epigenetic modifications are involved in cell reprogramming and totipotency in response to stress. To increase microspore embryogenesis (ME) efficiency in bread wheat, the effect of the histone deacetylase inhibitor trichostatin A (TSA) has been examined in two cultivars of wheat with different microspore embryogenesis response. Diverse strategies were assayed using 0-0.4 mu M TSA as a single induction treatment and after or simultaneously with cold or mannitol stresses. The highest efficiency was achieved when 0.4 mu M TSA was applied to anthers for 5 days simultaneously with a 0.7 M mannitol treatment, producing a four times greater number of green DH plants than mannitol. Ultrastructural studies by transmission electron microscopy indicated that mannitol with TSA and mannitol treatments induced similar morphological changes in early stages of microspore reprogramming, although TSA increased the number of microspores with 'star-like' morphology and symmetric divisions. The effect of TSA on the transcript level of four ME marker genes indicated that the early signaling pathways in ME, involving the TaTDP1 and TAA1b genes, may be mediated by changes in acetylation patterns of histones and/or other proteins.
  • Autores: Ahechu Garayoa, Patricia; Rotellar Sastre, Fernando; Valentí Azcarate, Víctor (Autor de correspondencia)
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.30 N° 10 2020 págs. 4127 - 4128
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia); Vilarrasa, N.; Poyato, F.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.9 N° 9 2020 págs. 2834
    Resumen
    The prevalence of obesity is rapidly rising in Spain. The Awareness, Care and Treatment in Obesity Management-An International Observation (ACTION-IO) study (NCT03584191) was an international cross-sectional survey conducted to identify the perceptions, attitudes, behaviors, and barriers to obesity management for people with obesity (PwO) and healthcare professionals (HCPs); results from Spain are presented. In Spain, 1500 PwO (body mass index >= 30 kg/m(2)based on self-reported height and weight) and 306 HCPs (in direct patient care for >= 2 years) completed the survey. Fewer PwO (59%) than HCPs (93%) agreed that obesity is a chronic disease. Most PwO (80%) assumed complete responsibility for their own weight loss, whilst 19% of HCPs placed the responsibility on PwO. One-fifth of PwO stated they began struggling with weight before age 15. The mean delay in discussing weight for the first time with an HCP was 6 years. Only 24% of HCPs thought their patients were motivated to lose weight, whilst 45% of PwO reported being motivated. Of the 67% of PwO who had discussed their weight with an HCP in the last 5 years, 66% had been formally diagnosed with obesity. Our Spanish dataset reveals discrepancies in the perceptions and attitudes between PwO and HCPs, thus highlighting the need to improve education about obesity and its clinical management.
  • Autores: Lara, J. P.; Compañ, A.; Vargas, J. A.; et al.
    Revista: EDUCACION MEDICA
    ISSN 1575-1813 Vol.21 N° 6 2020 págs. 397 - 402
    Resumen
    En este documento se refieren las bases legales nacionales y, más en concreto, las autonómicas andaluzas que dan respaldo a la figura del profesor contratado doctor vinculado y a la posibilidad de convocar las plazas correspondientes en las facultades de medicina de las universidades públicas españolas. Se exponen, asimismo, las características asistenciales y académicas que deben darse para llevar a cabo la convocatoria pública de dichas plazas. Se resume, a continuación, cuál es la situación actual existente en relación con dicha figura del profesorado en las facultades de medicina españolas. Se analizan también las ventajas y las posibles limitaciones que actualmente se derivan de contar con profesores contratados doctores vinculados y ello tanto para los médicos especialistas eventualmente interesados en optar a una de estas plazas como para el centro sanitario y la facultad de medicina correspondientes. Finalmente, se reseña la posible utilidad del documento elaborado por la Conferencia Nacional de Decanos de Facultades de Medicina de España (CNDFME) en la Asamblea General que se celebró en la Facultad de Medicina de Oviedo del 17 al 19 de mayo del 2018 y actualizado en marzo de 2020.
  • Autores: Fruhbeck Martínez, Gema; Balaguer, I. ; Mendez-Gimenez, L. ; et al.
    Revista: CELLS
    ISSN 2073-4409 Vol.9 N° 6 2020 págs. 1403
    Resumen
    Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H2O2), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-¿, and particularly TGF-ß1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-ß1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-ß1-induced ER stress in visceral adipocytes. Owing to its "peroxiporin" properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.
  • Autores: Goossens, G. H. (Autor de correspondencia); Dicker, D. ; Farpour-Lambert, N. J.; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.13 N° 4 2020 págs. 439 - 452
    Resumen
    Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.
  • Autores: Pasquali, R. (Autor de correspondencia); Casanueva, F.; Haluzík, M.; et al.
    Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
    ISSN 0804-4643 Vol.182 N° 1 2020 págs. G1 - G32
    Resumen
    Obesity is an emerging condition, with a prevalence of -20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.
  • Autores: Llorente Gómez de Segura, Ignacio; Catalán Goñi, Victoria; Gómez Ambrosi, Javier; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.50 2020 págs. 12 - 13
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramirez, B. ; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.50 2020 págs. 13 - 14
  • Autores: Perdomo Zelaya, Carolina María; Fruhbeck Martínez, Gema; Escalada San Martín, Francisco Javier (Autor de correspondencia)
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 3 2019 págs. 677
    Resumen
    Non-alcoholic fatty liver disease (NAFLD) is a major global health threat due to its growing incidence and prevalence. It is becoming the leading cause of liver disease in addition to its strong association with cardio-metabolic disease. Therefore, its prevention and treatment are of strong public interest. Therapeutic approaches emphasize lifestyle modifications including physical activity and the adoption of healthy eating habits that intend to mainly control body weight and cardio-metabolic risk factors associated with the metabolic syndrome. Lifestyle interventions may be reinforced by pharmacological treatment in advanced stages, though there is still no registered drug for the specific treatment of NAFLD. The purpose of this review is to assess the evidence available regarding the impact of dietary recommendations against NAFLD, highlighting the effect of macronutrient diet composition and dietary patterns in the management of NAFLD.
  • Autores: Martinez, S. B. (Autor de correspondencia); Jauregui, E. P.; Escalada San Martín, Francisco Javier
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.66 N° 1 2019 págs. 62 - 68
    Resumen
    The important prevalence and morbidity of obesity has generated an increase in bariatric surgery. It has a positive effect in obesity-related comorbidities. However, it's detrimental to bone health. The underline pathophysiological mechanisms are complex and heterogeneous. The knowledge of these factors may lead us to develop an adequate therapeutic intervention.
  • Autores: Gargallo Vaamonde, Javier; Fruhbeck Martínez, Gema; Salvador Rodríguez, Javier
    Revista: CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH
    ISSN 2451-9650 Vol.4 2019 págs. 75 - 82
    Resumen
    Recently marketed antiobesity medications have improved the obesity therapeutic performance by promoting weight loss in patients treated with diet, physical activity and nutritional education. However, mean placebo-subtracted weight loss following treatment with phentermine, lorcaserin, liraglutide 3 mg or the combinations phentermine-topiramate and naltrexone-bupropion reaches 3¿10%. Although this weight reduction translates into significant benefits in obesity comorbidities management, more weight reduction is needed to reduce the gap between conventional treatment and bariatric surgery. The new weekly GLP-1 receptor agonist, semaglutide, exhibits a powerful effect on body weight reduction showing better performance when compared with other members of the same family in diabetic patients. Biochemical engineering has produced diverse unimolecular peptides displaying GLP-1, glucagon and GIP agonist action that are being investigated in preclinical models and clinical trials, showing encouraging results regarding weight loss and treatment of obese comorbidities such as diabetes, dyslipidemia and liver steatosis. Other medications such as amylin analogs, and different agonists and antagonists of satiating and orexigenic neuronal pathways offer new approaches. The possibility of conjugating peptides such as GLP-1 or glucagon with glucocorticoids, estrogens or triiodothyronine to deliver selectively these hormones to tissues expressing receptors involved in energy balance control opens a new era in obesity therapy. Preclinical studies show that this targeting strategy allows achieving selective hormonal actions with prevention of adverse effects in other organs. Peripheral pharmacological approaches including stimulation of thermogenesis, activation of bile acid receptors, lipolysis stimulation and manipulation of gut microbiota may also take part of this unlimited universe of pharmacological options. Drug combinations of compounds acting on different pathways and through diverse mechanisms represent an excellent option to increase efficacy and improve long-term results when compared with strategies based in monotherapy.
  • Autores: Ezquerro Ezquerro, Silvia; Rodríguez Murueta-Goyena, Amaia; Portincasa, P.; et al.
    Revista: CURRENT MEDICINAL CHEMISTRY
    ISSN 0929-8673 Vol.26 N° 19 2019 págs. 3593 - 3612
    Resumen
    Background: Obesity is a major health problem that has become a global epidemic. Overweight and obesity are commonly associated with the development of several pathologies, such as insulin resistance, cardiovascular diseases, sleep apnea and several types of cancer, which can lead to further morbidity and mortality. An increased abdominal adiposity renders overweight and obese individuals more prone to metabolic and cardiovascular problems. Objective: This Review aims to describe the dietary strategies to deal with excess adiposity given the medical, social and economic consequences of obesity. Methods: One hundred and eighty-five papers were included in the present Review. Results: Excess adiposity leads to several changes in the biology, morphology and function of the adipose tissue, such as adipocyte hypertrophy and hyperplasia, adipose tissue inflammation and fibrosis and an impaired secretion of adipokines, contributing to the onset of obesity-related comorbidities. The first approach for obesity management and prevention is the implementation of a diet combined with physical activity. The present review summarizes the compelling evidence showing body composition changes, impact on cardiometabolism and potential adverse effects of very-low calorie, low-and high-carbohydrate, high-protein or low-fat diets. The use of macronutrients during the preprandial and postprandial state has been also reviewed to better understand the metabolic changes induced by different dietary interventions. Conclusion: Dietary changes should be individualised, tailored to food preferences and allow for flexible approaches to reducing calorie intake in order to increase the motivation and compliance of overweight and obese patients.
  • Autores: Pérez Pevida, Belén (Autor de correspondencia); Escalada San Martín, Francisco Javier; Miras, A. D.; et al.
    Revista: FRONTIERS IN ENDOCRINOLOGY
    ISSN 1664-2392 Vol.10 2019
    Resumen
    Type 2 diabetes prevalence is increasing dramatically worldwide. Metabolic surgery is the most effective treatment for selected patients with diabetes and/or obesity. When compared to intensive medical therapy and lifestyle intervention, metabolic surgery has shown superiority in achieving glycemic improvement, reducing number of medications and cardiovascular risk factors, which translates in long-term benefits on cardiovascular morbidity and mortality. The mechanisms underlying diabetes improvement after metabolic surgery have not yet been clearly understood but englobe a complex interaction among improvements in beta cell function and insulin secretion, insulin sensitivity, intestinal gluconeogenesis, changes in glucose utilization, and absorption by the gut and changes in the secretory pattern and morphology of adipose tissue. These are achieved through different mediators which include an enhancement in gut hormones release, especially, glucagon-like peptide 1, changes in bile acids circulation, gut microbiome, and glucose transporters expression. Therefore, this review aims to provide a comprehensive appraisal of what is known so far to better understand the mechanisms through which metabolic surgery improves glycemic control facilitating future research in the field.
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 9 2019 págs. 2129
    Resumen
    Leptin, the product of the ob gene, was originally described as a satiety factor, playing a crucial role in the control of body weight. Nevertheless, the wide distribution of leptin receptors in peripheral tissues supports that leptin exerts pleiotropic biological effects, consisting of the modulation of numerous processes including thermogenesis, reproduction, angiogenesis, hematopoiesis, osteogenesis, neuroendocrine, and immune functions as well as arterial pressure control. Nitric oxide (NO) is a free radical synthesized from L-arginine by the action of the NO synthase (NOS) enzyme. Three NOS isoforms have been identified: the neuronal NOS (nNOS) and endothelial NOS (eNOS) constitutive isoforms, and the inducible NOS (iNOS). NO mediates multiple biological effects in a variety of physiological systems such as energy balance, blood pressure, reproduction, immune response, or reproduction. Leptin and NO on their own participate in multiple common physiological processes, with a functional relationship between both factors having been identified. The present review describes the functional relationship between leptin and NO in different physiological processes.
  • Autores: Landecho Acha, Manuel Fortún; Tuero Ojanguren, Carlota; Valentí Azcarate, Víctor; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 11 2019 págs. 2664
    Resumen
    Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
  • Autores: Paslakis, G.; Aguera, Z. ; Granero, R.; et al.
    Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
    ISSN 0303-7207 Vol.497 2019
    Resumen
    Anorexia nervosa (AN) is a severe eating disorder accompanied by alterations in endocrinological circuits and deficits in neuropsychological performance. In this study, a series of appetite-regulating hormones (ghrelin, leptin, cholecystokinin, PYY, adiponectin, and visfatin) were measured under fasting conditions in female patients with AN and female healthy controls. All of the participants also underwent a battery of neuropsychological assessment [namely the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test (WCST), and the Stroop Color and Word Test (SCWT)]. As the main finding, we found that higher ghrelin levels predict better performance in the IGT. Ghrelin may be a putative mediator of decision-making, a finding that has not been described so far. The role of ghrelin in decision-making can only be described as speculative, as there are hardly any additional evidence-based data published up to date. Further studies are warranted.
  • Autores: James, W. P. T. (Autor de correspondencia); Johnson, R. J.; Speakman, J. R.; et al.
    Revista: JOURNAL OF INTERNAL MEDICINE
    ISSN 0954-6820 Vol.285 N° 5 2019 págs. 533 - 549
    Resumen
    Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300000years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50000-100000years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.
  • Autores: Di Ciaula, A.; Garruti, G. ; Fruhbeck Martínez, Gema; et al.
    Revista: CURRENT MEDICINAL CHEMISTRY
    ISSN 0929-8673 Vol.26 N° 19 2019 págs. 3620 - 3638
    Resumen
    Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans. There is a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and fiber, olive oil and fish (omega-3 fatty acids) consumption, vegetable protein intake, fruit, coffee, moderate alcohol consumption and vitamin C supplementation exert a protective role. The effect of some confounding factors (e.g., physical activity) cannot be ruled out, but general recommendations about the multiple beneficial effects of diet on cholesterol gallstones must be kept in mind, in particular in groups at high risk of gallstone formation.
  • Autores: Yarnoz-Esquiroz, P. (Autor de correspondencia); Lacasa Arregui, Carlos; Riestra, M. ; et al.
    Revista: EUROPEAN EATING DISORDERS REVIEW
    ISSN 1072-4133 Vol.27 N° 6 2019 págs. 581 - 602
    Resumen
    Objective The aim of this review is to analyse the studies about cost and clinical implications that malnutrition causes in the Spanish hospitals. Material and methods The review of the literature was carried out through a bibliographic search in Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and analyse the cost of treatment of malnourished and anorexia nervosa (AN) patients Results Seventeen studies with economic data related to malnutrition were included. The employment of a nutritional screening is the first tool to determinate the prevalence. Malnutrition is related to an incremental cost due to a longer hospital stay, expensive treatment, and higher rate of readmissions. Malnourished patients present more clinical complications, more infections, and higher mortality. No studies were found with economic data of AN in Spain. Conclusions The prevalence of malnutrition is over 20%, with the elderly patients being the most affected. Nutritional screening is not implanted in all Spanish hospitals in spite of its proven cost-effectiveness. The cost and the clinical implications of malnutrition make this disease a health national problem. The knowledge of the real cost of AN treatment would increase the interest of public institutions on the development of specific Nutritional Screening tools for an early detection of AN.
  • Autores: Moncada Durruti, Rafael (Autor de correspondencia)
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.42 N° 3 2019 págs. 355 - 356
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Rotellar Sastre, Fernando; Valentí Azcarate, Víctor
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.111 N° 11 2019 págs. 896 - 897
    Resumen
    We have read with great interest the study by Vera MC et al. on the intrasplenic transplantation of hepatocytes from donors receiving the carcinogenic drugs diethylnitrosamine (DEN) and 2-actylaminofluorene (2-AAF). The most important conclusion of the study is that there were no signs of tumor progression in the recipient liver at seven and 60 days after hepatocellular transplantation and no differences were found in the animals with healthy hepatocyte transplants.
  • Autores: Gargallo Vaamonde, Javier; Perdomo Zelaya, Carolina María; De la Higuera López-Frías, Magdalena; et al.
    Revista: EXPERT OPINION ON PHARMACOTHERAPY
    ISSN 1465-6566 Vol.20 N° 4 2019 págs. 367 - 371
  • Autores: Unamuno Iñurritegui, Xabier; Portincasa, P.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN 2213-8587 Vol.7 N° 10 2019 págs. 743 - 745
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia)
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.66 N° 5 2019 págs. 275 - 277
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Busetto, L.; Dicker, D. ; et al.
    Revista: OBESITY FACTS
    ISSN 1662-4025 Vol.12 N° 2 2019 págs. 131 - 136
    Resumen
    Obesity is a frequent, serious, complex, relapsing, and chronic disease process that represents a major public health problem. The coining of obesity as an adiposity-based chronic disease (ABCD) is of particular relevance being in line with EASO's proposal to improve the International Classification of Diseases ICD-11 diagnostic criteria for obesity based on three dimensions, namely etiology, degree of adiposity, and health risks. The body mass index as a unique measurement of obesity does not reflect the whole complexity of the disease. Obesity complications are mainly determined by 2 pathological processes, i.e., physical forces (fat mass disease) as well as endocrine and immune responses (sick fat disease), which are embedded in a cultural and physical context leading to a specific ABCD stage. (c) 2019 The Author(s) Published by S. Karger AG, Basel
  • Autores: Reyes-Garcia, R. (Autor de correspondencia); Moreno-Perez, O. ; Tejera-Perez, C. ; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.66 N° 7 2019 págs. 443 - 458
    Resumen
    Objective: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endo-crinology. Methods: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.
  • Autores: Caterson, I. D. (Autor de correspondencia); Alfadda, A. A.; Auerbach, P. ; et al.
    Revista: DIABETES OBESITY AND METABOLISM
    ISSN 1462-8902 Vol.21 N° 8 2019 págs. 1914 - 1924
    Resumen
    Aims Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). Materials and methods An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care. Results A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required. Conclusions Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.
  • Autores: Folgueira, C.; Beiroa, D.; Porteiro, B. ; et al.
    Revista: NATURE METABOLISM
    ISSN 2522-5812 Vol.1 N° 8 2019 págs. 811 - 829
    Resumen
    Dopamine signalling is a crucial part of the brain reward system and can affect feeding behaviour. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after the onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the central nervous system to regulate energy balance.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 2 2019 págs. E454
    Resumen
    Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ¿1.0 can be considered normal, a ratio of ¿0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.
  • Autores: Ceperuelo-Mallafre, V.; Llaurado, G. ; Keiran, N. ; et al.
    Revista: DIABETES CARE
    ISSN 0149-5992 Vol.42 N° 10 2019 págs. 1956 - 1965
    Resumen
    OBJECTIVE To determine the potential use of baseline circulating succinate to predict type 2 diabetes remission after bariatric surgery. RESEARCH DESIGN AND METHODS Forty-five obese patients with diabetes were randomly assigned to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or laparoscopic greater curvature plication. Anthropometric parameters were evaluated, and a complete biochemical analysis including circulating serum succinate concentrations was performed at baseline and 1 year after surgery. The results were externally validated in a second cohort including 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria. RESULTS Succinate baseline concentrations were an independent predictor of diabetes remission after bariatric surgery. Patients achieving remission after 1 year had lower levels of baseline succinate (47.8 [37.6-64.6] mu mol/L vs. 64.1 [52.5-82.9] mu mol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4-82.4] mu mol/L vs. 46.0 [35.8-65.3] mu mol/L, P = 0.005). In multivariate analysis, the best logistic regression model showed that baseline succinate (odds ratio [OR] 11.3, P = 0.031) and the type of surgery (OR 26.4, P = 0.010) were independently associated with remission. The C-statistic for this model was 0.899 (95% CI 0.809-0.989) in the derivation cohort, which significantly improved the prediction of remission compared with current available scores, and 0.729 (95% CI 0.612-0.846) in the validation cohort. Interestingly, patients had a different response to the type of surgery according to baseline succinate, with significant differences in remission rates. CONCLUSIONS Circulating succinate is reduced after bariatric surgery. Baseline succinate levels have predictive value for diabetes remission independently of previously described presurgical factors and improve upon the current available scores to predict remission.
  • Autores: Martinaitis, L.; Tuero Ojanguren, Carlota; Landecho Acha, Manuel Fortún; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.111 N° 5 2019 págs. 371 - 377
    Resumen
    Purpose: to assess the long-term benefits of bariatric surgery in super-obese (body mass index [BMI] = 50) and in elderly obese (age > 60 years) populations. Methods: one hundred and twenty one patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy in a university hospital were retrospectively subdivided into the following groups: BMI < 50 vs = 50 and age < 60 vs = 60 years. Weight loss, body composition and comorbidity outcomes were registered after one and six months and one, two, three and five years with 100%, 93%, 89%, 80%, 75% and 60% successful follow-up. Results: the percentage of excess BMI loss (% EBMIL) was comparable between BMI groups and age groups and the difference in the long-term follow up was not statistically significant (p > 0.05). Complication rates, comorbidity resolution, reduction in body fat and increase in fat-free mass were comparable between BMI groups and age groups. Gastric bypass resulted in a greater weight loss compared to sleeve gastrectomy. The % EBMIL was 65.2% vs 46.7% (p = 0.002), 65.8% vs 44.9% (p = 0.004), 64.4% vs 30.5% (p = 0.001), 55.6% vs 17.6% (p = 0.016) at one, two, three and five years postoperative, respectively. Similarly, in the super-obese group, weight loss was more pronounced after gastric bypass versus sleeve gastrectomy. Conclusions: bariatric surgery in super-obese and elderly populations is an effective and safe weight loss measure with a good comorbidity resolution in the long-term. Gastric bypass is superior to sleeve gastrectomy in terms of long-term weight loss and comorbidity resolution in all the groups investigated.
  • Autores: Lara, J. P. (Autor de correspondencia); Compan, A.; Vargas-Nunez, J. A.; et al.
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN 0014-2565 Vol.219 N° 2 2019 págs. 84 - 89
    Resumen
    The significant and progressive reduction in the number of permanent teachers in medical schools (professor, associate professor and assistant professor) is a reason for concern for the National Conference of Deans. This reduction will intensify in the coming decade (2017-2026). Forty-three percent of the permanent faculty will retire, as will 55% of the faculty linked to clinical areas, 34% of the faculty not linked to clinical areas and 32% of the faculty of basic areas. This deficit is significant now, and, in a few years, the situation wilt be unsustainable, especially in the clinical areas. This report reveals the pressing need to adopt urgent measures to alleviate the present situation and prevent a greater problem. The training of future physicians, immediately responsible for the health of our society, depends largely on the theoretical and practical training taught in medical schools, with the essential collaboration of healthcare institutions. Paradoxically, while the number of teachers decreases substantially, there is an exponential increase in the number of medical schools and students who are admitted every year without academic or healthcare justification.
  • Autores: Izaguirre Ascargorta, Maitane; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.8 N° 4 2019 págs. 479
    Resumen
    Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
  • Autores: Morillas, C. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Palomares, R.; et al.
    Revista: DIABETES THERAPY
    ISSN 1869-6953 Vol.10 N° 5 2019 págs. 1893 - 1907
    Resumen
    Introduction The aim of this Delphi study is to unveil the management of patients with type 2 diabetes (T2D) and different levels of complexity in the clinical practice in Spain. Methods Based on the common management practices of T2D profiles reported by Spanish endocrinologists, a Delphi questionnaire of 55 statements was developed and responded to by a national panel (n = 101). Results A consensus was reached for 30 of the 55 statements. Regarding overweight patients inadequately controlled with metformin, treatment with a sodium-glucose transport protein 2 inhibitor (SGLT2-I) is preferred over treatment with a dipeptidyl peptidase-4 inhibitor (DPP4-I). If the patient is already being treated with a DPP4-I, an SGLT2-I is added on to the treatment regimen rather than replacing the DPP4-I. Conversely, if the treatment regimen includes a sulfonylurea, it is usually replaced by other antihyperglycemic agents. Current treatment trends in uncontrolled obese patients include the addition of an SGLT2-I or a glucagon-like peptide-1 receptor agonist (GLP1-RA) to background therapy. When the glycated hemoglobin target is not reached, triple therapy with metformin + GLP1-RA + SGLT2-I is initiated. Although SGLT2-Is are the treatment of choice in patients with T2D and heart failure or uncontrolled hypertension, no consensus was reached regarding the preferential use of SGLT2-Is or GLP1-RAs in patients with established cardiovascular disease. Conclusion Consensus has been reached for a variety of statements regarding the management of several T2D profiles. Achieving a more homogeneous management of complex patients with T2D may require further evidence and a better understanding of the key drivers for treatment choice. Funding Logistic support was provided by ESTEVE Pharmaceuticals S.A Spain.
  • Autores: Pérez Pevida, Belén (Autor de correspondencia); Núñez Córdoba, Jorge María; Romero, S.; et al.
    Revista: JOURNAL OF TRANSLATIONAL MEDICINE
    ISSN 1479-5876 Vol.17 2019 págs. 48
    Resumen
    Background and aims: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. Methods: We studied 447 subjects with overweight/obesity with a fasting glucose value <= 5.5 mmol l(-1) (99 mg dl(-1)) and BMI >= 25 kg/m(2) who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level >= 7.8 mmol l(-1) (140 mg dl(-1)) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. Results: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. Conclusions: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT.
  • Autores: Anon-Hidalgo, J.; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: AGING-US
    ISSN 1945-4589 Vol.11 N° 6 2019 págs. 1733 - 1744
    Resumen
    Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta (TGF beta) superfamily which declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41-50 y group and a decline in the elder groups (61-70 and 71-80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat-free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and IogGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging.
  • Autores: Becerril Mañas, Sara (Autor de correspondencia); Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: GENES
    ISSN 2073-4425 Vol.10 N° 3 2019 págs. 184
    Resumen
    The role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxide synthase (iNOS) deletion on inflammation and ECM remodeling in the liver of ob/ob mice, since a functional relationship between leptin and iNOS has been described. The expression of molecules involved in inflammation and ECM remodeling was analyzed in the liver of double knockout (DBKO) mice simultaneously lacking the ob and the iNOS genes. Moreover, the effect of leptin was studied in the livers of ob/ob mice and compared to wild-type rodents. Liver inflammation and fibrosis were increased in leptin-deficient mice. As expected, leptin treatment reverted the obesity phenotype. iNOS deletion in ob/ob mice improved insulin sensitivity, inflammation, and fibrogenesis, as evidenced by lower macrophage infiltration and collagen deposition as well as downregulation of the proinflammatory and profibrogenic genes including Tnc. Circulating TNC levels were also decreased. Furthermore, leptin upregulated TNC expression and release via NO-dependent mechanisms in AML12 hepatic cells. iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD.
  • Autores: Steward, T. ; Mestre-Bach, G.; Granero, R. ; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.9 N° 1 2019 págs. 7910
    Resumen
    Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.
  • Autores: Christou, G. A. ; Katsiki, N.; Blundell, J. ; et al.
    Revista: OBESITY REVIEWS
    ISSN 1467-7881 Vol.20 N° 6 2019 págs. 805 - 815
    Resumen
    Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.
  • Autores: Grattagliano, I. ; Montezinho, L. P.; Oliveira, P. J.; et al.
    Revista: BIOCHEMICAL PHARMACOLOGY
    ISSN 0006-2952 Vol.160 2019 págs. 34 - 45
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extra-cellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.
  • Autores: Unamuno Iñurritegui, Xabier; Izaguirre Ascargorta, Maitane; Gómez Ambrosi, Javier; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 9 2019 págs. 2069
    Resumen
    Bariatric surgery remains the most effective option for achieving important and sustained weight loss. We explored the effects of Roux-en-Y gastric bypass (RYGB) on the circulating levels of adiponectin, leptin, and the adiponectin/leptin (Adpn/Lep) ratio in patients with obesity and type 2 diabetes (T2D). Twenty-five T2D volunteers undergoing RYGB were included in the study, and further subclassified as patients that responded or not to RYBG, regarding remission of T2D. Anthropometric and biochemical variables were evaluated before and after RYGB. Obese patients with T2D exhibited an increase (p < 0.0001) in the Adpn/Lep ratio after RYGB. Changes in the Adpn/Lep ratio correlated better with changes in anthropometric data (p < 0.001) than with the variations of adiponectin or leptin alone. Multiple regression analysis revealed that the change in the Adpn/Lep ratio in patients with T2D was an independent predictor of the changes in body mass index (p < 0.001) and body fat percentage (p = 0.022). However, the Adpn/Lep ratio did not differ between individuals with or without T2D remission after RYGB. In summary, the current study demonstrated that after weight and body fat loss following RYGB, the Adpn/Lep ratio increased in patients with obesity and T2D.
  • Autores: Anon-Hidalgo, J.; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN 2077-0383 Vol.8 N° 6 2019 págs. 878
    Resumen
    Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.
  • Autores: Hurtado-Pardo, L.; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Antoñanzas Pérez, Javier; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.111 N° 2 2019 págs. 87 - 93
    Resumen
    Background: the aim of the present study was to analyze the clinicopathological features of patients undergoing pancreatic surgical resections due to cystic neoplasms of the pancreas. Material and methods: demographic data, form of presentation, radiologic images and location of the tumors within the pancreas were analyzed. Data was also collected on the type of surgery (open/laparoscopic), postoperative complications and their severity and oncologic outcomes. Results: eighty-two pancreatic resections were performed. The mean age of patients was 57 years and 49 (59%) were female. Forty-one tumors (50%) were incidental and the most frequent symptoms in the group of symptomatic patients were abdominal pain (63.4%) and weight loss (36.5%). Thirty-two tumors (39%) were located in the tail of the pancreas, 25 (30.5%) in the head and 20 (24.4%) in the body. Thirty-nine (47.5%) distal pancreatectomies, 16 central, ten duodenal pancreatectomies and one enucleation were performed; 40 (48.5%) were carried out laparoscopically. Mean hospital stay was ten days and eight patients (7%) experienced severe complications, one was a pancreatic fistula. Sixty-six tumors (80.5%) were recorded as non-invasive and 16 (19.5%) as invasive: seven intraductal mucinous papillary tumors, one cystic mucinous tumor, four solid pseudopapillary tumors and four cystic neuroendocrine tumors. There was a median follow-up of 64 months; disease-free survival at five and ten years was 97.4% in the patients with non-invasive tumors and 84.6% and 70.5% in the invasive tumors group (p < 0.01). Conclusions: fifty percent of cystic neoplasms of the pancreas are incidental. Two phenotypes exist, invasive and non-invasive.
  • Autores: Ortega, F. J. (Autor de correspondencia); Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
    Revista: FASEB JOURNAL
    ISSN 0892-6638 Vol.33 N° 8 2019 págs. 9656 - 9671
    Resumen
    During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-beta, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagln2 using the adipocyte protein 2 promoter disclosed remarkable sex-dependent variations, in which females displayed healthy obesity and hypertrophied adipocytes but preserved insulin sensitivity, and males exhibited physiologic changes suggestive of defective AT expandability, including increased number of small adipocytes, activation of immune cells, mitochondrial dysfunction, and impaired metabolism together with decreased insulin sensitivity. The metabolic relevance and sexual dimorphism of TAGLN2 was also outlined by genetic variants that may modulate its expression and are associated with obesity and the risk of ischemic heart disease in men. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to the obese phenotype in a gender-dependent manner.-Ortega, F. J., Moreno-Navarrete, J. M., Mercader, J. M., Gomez-Serrano, M., Garcia-Santos, E., Latorre, J., Lluch, A., Sabater, M., Caballano-Infantes, E., Guzman, R., Macias-Gonzalez, M., Buxo, M., Girones, J., Vilallonga, R., Naon, D., Botas, P., Delgado, E., Corella, D., Burcelin, R., Fruhbeck, G., Ricart, W., Simo, R., Castrillon-Rodriguez, I., Tinahones, F. J., Bosch, F., Vidal-Puig, A., Malagon, M. M., Peral, B., Zorzano, A., Fernandez-Real, J. M. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.
  • Autores: Sanchez, M. ; Sanchez, E.; Hernandez, M.; et al.
    Revista: NUTRIENTS
    ISSN 2072-6643 Vol.11 N° 6 2019 págs. 1359
    Resumen
    There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables. ClinTrials.gov Identifier: NCT03228459.
  • Autores: Ezquerro, S.; Mocha, F.; Fruhbeck Martínez, Gema; et al.
    Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
    ISSN 0021-972X Vol.104 N° 1 2019 págs. 21 - 37
    Resumen
    CONTEXT: Human obesity is associated with increased circulating TNF-¿, a proinflammatory cytokine that induces hepatocyte cell death. OBJECTIVE: The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-¿-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated. DESIGN, SETTINGS, AND PARTICIPANTS: Plasma ghrelin isoforms and TNF-¿ were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-¿-induced cell death was determined in vitro in human HepG2 hepatocytes. RESULTS: Circulating TNF-¿ and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-¿-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-¿-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR. CONCLUSIONS: Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-¿-induced hepatocyte apoptosis, autophagy, and pyroptosis.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 35 - 35
  • Autores: Lujan Colas, Juan; Tuero Ojanguren, Carlota; Moncada Durruti, Rafael; et al.
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.29 N° Suppl.5 2019 págs. 302 - 302
  • Autores: Gómez Ambrosi, Javier; González Crespo, Ignacio; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 147 - 147
  • Autores: Catalán Goñi, Victoria; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 150
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 148 - 149
  • Autores: Valentí Azcarate, Víctor; Tuero Ojanguren, Carlota; Moncada Durruti, Rafael; et al.
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.29 N° Supl. 5 2019 págs. 727 - 727
  • Autores: Ezquerro, S. ; Mendez-Gimenez, L.; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 55 - 56
  • Autores: Ezquerro, S. ; Mocha, F.; Fruhbeck Martínez, Gema; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.49 N° Supl. 1 2019 págs. 79 - 80
  • Autores: Mendez-Gimenez, L.; Ezquerro, S.; da Silva, I. V. ; et al.
    Revista: FRONTIERS IN CHEMISTRY
    ISSN 2296-2646 Vol.6 2018 págs. 99
    Resumen
    Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in alpha, beta, delta, epsilon, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic beta-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced beta-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in beta-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of aquaporins in the physiology and pathophysiology of the pancreas, highlighting the role of pancreatic AQP7 as a novel player in the control of b-cell function and a potential anti-diabetic-drug.
  • Autores: Vecchie, A.; Dallegri, F. ; Carbone, F.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN 0953-6205 Vol.48 2018 págs. 6 - 17
    Resumen
    The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity.
  • Autores: Unamuno, X.; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° 9 2018 págs. e12997
    Resumen
    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.
  • Autores: Ahechu Garayoa, Patricia; Zozaya Larequi, Gabriel Nicolás; Martí Cruchaga, Pablo; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN 1664-3224 Vol.9 2018 págs. 2918
    Resumen
    Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1 beta and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
  • Autores: Pedro-Botet, J. (Autor de correspondencia); Ascaso, J. F.; Barrios, V. ; et al.
    Revista: DIABETES, METABOLIC SYNDROME AND OBESITY
    ISSN 1178-7007 Vol.11 2018 págs. 683 - 697
    Resumen
    Metabolic syndrome (MetS), a disorder with a high and growing prevalence, is a recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes. It is a constellation of clinical and metabolic risk factors that include abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Unfortunately, MetS is typically underrecognized, and there is great heterogeneity in its management, which can hamper clinical decision-making and be a barrier to achieving the therapeutic goals of CVD and diabetes prevention. Although no single treatment for MetS as a whole currently exists, management should be targeted at treating the conditions contributing to it and possibly reversing the risk factors. All this justifies the need to develop recommendations that adapt existing knowledge to clinical practice in our healthcare system. In this regard, professionals from different scientific societies who are involved in the management of the different MetS components reviewed the available scientific evidence focused basically on therapeutic aspects of MetS and developed a consensus document to establish recommendations on therapeutic goals that facilitate their homogenization in clinical decision-making.
  • Autores: Landecho Acha, Manuel Fortún; Inigo-Morras, E.; Valentí Azcarate, Víctor (Autor de correspondencia)
    Revista: OBESITY SURGERY
    ISSN 0960-8923 Vol.28 N° 10 2018 págs. 3299 - 3300
  • Autores: Catalán Goñi, Victoria (Autor de correspondencia); Salvador Rodríguez, Javier; Fruhbeck Martínez, Gema; et al.
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN 1137-6627 Vol.41 N° 2 2018 págs. 287 - 289
  • Autores: Silva Frojan, Camilo (Autor de correspondencia); Llavero Valero, María; Varo Cenarruzabeitia, Nerea; et al.
    Revista: ANNALES D ENDOCRINOLOGIE
    ISSN 0003-4266 Vol.79 N° 2 2018 págs. 85 - 86
  • Autores: Fruhbeck Martínez, Gema; Badimon, L.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 6 - 7
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Kiortsis, D. N.; Catalán Goñi, Victoria
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN 2213-8587 Vol.6 N° 3 2018 págs. 164 - 166
  • Autores: Unamuno, X.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET
    ISSN 0140-6736 Vol.392 N° 10161 2018 págs. 2239 - 2240
  • Autores: Spittal, M. J.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN 2213-8587 Vol.6 N° 3 2018 págs. 161 - 163
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: ADIPOCYTE
    ISSN 2162-3945 Vol.7 N° 1 2018 págs. 57 - 62
    Resumen
    Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
  • Autores: Burgos-Ramos, E.; Canelles, S. ; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
    ISSN 0303-7207 Vol.470 2018 págs. 48 - 59
    Resumen
    Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L with no changes in PF. Acetyl-CoA carboxylase-beta mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-lb expression and mitochondrial complexes augmented in L These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. (C) 2017 Elsevier B.V. All rights reserved.
  • Autores: Travez, A.; Rabanal-Ruiz, Y. ; Lopez-Alcala, J. ; et al.
    Revista: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (ONLINE)
    ISSN 1582-4934 Vol.22 N° 11 2018 págs. 5648 - 5661
    Resumen
    Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane-binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled-coil protein-2 (NECC2), in adipocytes. Studies in 3T3-L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co-immunoprecipitated with caveolin-1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin-activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin-induced phosphorylation of Akt and ERK2. Finally, an up-regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3-L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: INTERNATIONAL JOURNAL OF OBESITY
    ISSN 0307-0565 Vol.42 N° 8 2018 págs. 1458 - 1470
    Resumen
    Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg(-1) day(-1)) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.
  • Autores: Cheng, Y.; Monteiro, C.; Matos, A.; et al.
    Revista: CLINICAL EPIGENETICS (ONLINE)
    ISSN 1868-7083 Vol.10 2018 págs. 54
    Resumen
    BACKGROUND: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI¿>¿25 kg m-2) and normal weight (NW, BMI¿<¿25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. RESULTS: Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. CONCLUSIONS: Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
  • Autores: Fruhbeck Martínez, Gema; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN 0026-0495 Vol.87 2018 págs. 123 - 135
    Resumen
    Objective: Kallistatin plays an important role in the inhibition of inflammation, oxidative stress, fibrosis and angiogenesis. We aimed to determine the impact of kallistatin on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and oxidative stress. Methods: Samples obtained from 95 subjects were used in a case-control study. Circulating concentrations and expression levels of kallistatin as well as key inflammation, oxidative stress and extracellular matrix remodelling-related genes were analyzed. Circulating kallistatin concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB). The impact of kallistatin on lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-mediated inflammatory as well as oxidative stress signalling pathways was evaluated. Results: We show that the reduced (P < 0.00001) circulating levels of kallistatin in obese patients increased (P < 0.00001) after RYGB. Moreover, gene expression levels of SERPINA4, the gene coding for kallistatin, were down regulated (P < 0.01) in the liver from obese subjects with non-alcoholic fatty liver disease. Additionally, we revealed that kallistatin reduced (P < 0.05) the expression of inflammation-related genes (CCL2, IL1B, IL6, IL8, TNFA, TGFB) and, conversely, upregulated (P < 0.05) mRNA levels of ADIPOQ and KLF4 in human adipocytes in culture. Kallistatin inhibited (P < 0.05) LPS- and INF-alpha-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Furthermore, kallistatin also blocked (P < 0.05) TNF-alpha-mediated lipid peroxidation as well as NOX2 and HIF1A expression while stimulating (P < 0.05) the. expression of SIRT1 and FOXO1. Conclusions: These findings provide, for the first time, evidence of a novel role of kallistatin in obesity and its associated comorbidities by limiting adipose tissue inflammation and oxidative stress.
  • Autores: Antoñanzas Pérez, Javier; Álvarez-Cienfuegos Suárez, Francisco Javier; Hurtado-Pardo, L.; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN 1130-0108 Vol.110 N° 12 2018 págs. 768 - 774
    Resumen
    Objective: the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas. Material and methods: patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years. Results: the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05). Conclusions: intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.
  • Autores: Borras, J. G. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Cases, M. M. ; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.65 N° Supl.1 2018 págs. 1 - 8
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Halimi, S.; Senior, P. A. ; et al.
    Revista: DIABETES OBESITY AND METABOLISM
    ISSN 1462-8902 Vol.20 N° 12 2018 págs. 2860 - 2868
    Resumen
    Aim Materials and Methods To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100). A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged >= 18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) Results Conclusions The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (<= 3.9 mmol/L [<= 70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m(2): relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR >= 60 mL/min/1.73 m(2): RR 0.75 [95% CI 0.67-0.85]). For confirmed (<= 70 mg/dL [<= 3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups. Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (<= 3.9 and <3.0 mmol/L [<= 70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups.
  • Autores: Moreno-Navarrete, J. M.; Rodríguez Murueta-Goyena, Amaia; Becerril Mañas, Sara; et al.
    Revista: MOLECULAR NUTRITION AND FOOD RESEARCH
    ISSN 1613-4125 Vol.62 N° 2 2018
    Resumen
    Scope: To investigate intestinal markers of iron absorption in morbidly obese subjects according to glucose tolerance. Methods and results: Gene expression of both non-heme (SLC40A1 (ferroportin), SLC11A2) and heme iron (SLC46A1 (HCP1), HMOX1) transporters is analyzed in 38 small intestine tissue samples [11 with normal glucose tolerance, 14 with glucose intolerance (GI), and 13 with newly diagnosed type 2 diabetes (T2D)]. SLC40A1 (r = 0.43, p = 0.008) and SLC11A2 (r = 0.35, p = 0.03) mRNA levels are positively correlated with ferritin-to-hepcidin ratio and with fasting glucose, being significantly increased in patients with T2D. Only ferroportin is negatively associated with serum hepcidin (r = -0.617, p < 0.0001). In multivariate regression analysis, fasting glucose contributes independently to intestinal SLC40A1 (p = 0.009) and SLC11A2 (p = 0.04) variance after controlling for age, sex, and BMI. When circulating hepcidin is incorporated into the model, fasting glucose contributes significantly and independently to intestinal SLC40A1 (p = 0.02), but not to SLC11A2 (p = 0.07) variance. SLC46A1 and HMOX1 are similar in all groups. Conclusion: The expression of ferroportin and SLC11A2 is increased in the intestine of patients with T2D in association with iron stores and serum hepcidin levels. Increased intestinal iron absorption is a potential mechanism that could explain the increased body iron stores frequently observed in patients with T2D.
  • Autores: Gomez-Peralta, F. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Torre, E. M.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN 2530-0180 Vol.65 N° 10 2018 págs. 611 - 624
    Resumen
    Type 2 diabetes mellitus (DM2) has become a problem of global dimensions by their high and growing prevalence worldwide and the personal and economic costs associated with it. Correct treatment can reduce mortality and associated complications. New concepts have recently been included in routine clinical practice and have changed the algorithm of DM2 pharmacological therapy. Therefore, the Spanish Society of Diabetes (SED) entrusted to the Working Group of Consensus and Clinical Guidelines an update of the 2010 document Recommendations for Pharmacological Treatment of Hyperglycemia in Diabetes type 2. Novel aspects include nine characteristics to describe each drug group: efficiency, the risk of hypoglycemia, effects on body weight, the demonstrated effect in cardiovascular risk, nephroprotection, limitation of use in renal insufficiency, the rate of secondary effects, complexity and costs. Additionally, the document details combination options, and develop the start and adjustment of available injectable therapies. (C) 2018 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Twigg, S. M. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Stella, P. ; et al.
    Revista: DIABETES THERAPY
    ISSN 1869-6953 Vol.9 N° 5 2018 págs. 2043 - 2053
    Resumen
    To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. A post hoc patient-level meta-analysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin + oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA(1c)), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (< 65 and 65 years), body mass index (BMI; < 30 and 30 kg/m(2)), age at onset (< 40, 40-50, and > 50 years), and diabetes duration (< 10 and 10 years). Reduction in HbA(1c) was comparable between insulins, regardless of subgroup. The lower risk of 1 nocturnal (00:00-05:59 h) confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of 1 confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. Sanofi. Plain language summary available for this article.
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia); González Crespo, Ignacio; Catalán Goñi, Victoria; et al.
    Revista: CLINICAL NUTRITION
    ISSN 0261-5614 Vol.37 N° 2 2018 págs. 580 - 589
    Resumen
    Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomographi(CT), Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with Cr and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m(2) to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm(2), and then with lower precision with increasing body mass, exhibiting a moderate high correlation with Cri VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Autores: Pérez Pevida, Belén; Diaz-Gutierrez, J.; Miras, A. D.; et al.
    Revista: OBESITY
    ISSN 1930-7381 Vol.26 N° 4 2018 págs. 672 - 682
    Resumen
    ObjectiveThe objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). MethodsSubjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. ResultsSubjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. ConclusionsThese data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD.
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier; Estevez, M. G.; Ruiz-Canela, Miguel; et al.
    Revista: JOURNAL OF GASTROINTESTINAL SURGERY
    ISSN 1091-255X Vol.22 N° 4 2018 págs. 713 - 721
    Resumen
    Laparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment. Clinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013. Thirteen patients (12 F/1 M) underwent surgery. The median age was 32 years old, and their mean body mass index was 20.7 (range 14.7-25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24 months (range 2-240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and there were no conversions to open surgery. Median hospital stay was 3 days (range 2-14). Over a median follow-up of 117 months (range 45-185), nine patients had excellent results although two required endovascular procedures at 70 and 24 months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (> 70%), better results were obtained, with complete resolution of symptoms in 71% of cases. Laparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.
  • Autores: Gómez Ambrosi, Javier; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 191 - 192
  • Autores: Martín Rodríguez, Marina; Rodríguez Murueta-Goyena, Amaia; Gómez Ambrosi, Javier; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 207 - 208
  • Autores: Esquiroz, P. Y.; Langarica, A. S.; Rovira, N. V.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 209 - 209
  • Autores: Rodríguez Murueta-Goyena, Amaia; Mendez-Gimenez, L.; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 189 - 190
  • Autores: Tuero Ojanguren, Carlota; Granero Peiro, Lucia; Ahechu Garayoa, Patricia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 202
  • Autores: Landecho Acha, Manuel Fortún; Sunsundegui Seviné, Patricia; Beloqui Ruiz, Óscar María; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 210 - 211
  • Autores: Gonzalez-Borja, I. ; Martín Rodríguez, Marina; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 204 - 205
  • Autores: Ortega, F. J.; Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 67
  • Autores: Unamuno, X.; Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl.1 2018 págs. 193 - 194
  • Autores: Ibáñez Solano, Patricia; Vila, N. ; Santesteban, V.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 192
  • Autores: Ezquerro, S.; Mendez-Gimenez, L.; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 190
  • Autores: Esquiroz, P. Y. ; Lacasa Arregui, Carlos; Silva Frojan, Camilo; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 209 - 210
  • Autores: Tuero Ojanguren, Carlota; Granero Peiro, Lucia; Rotellar Sastre, Fernando; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 202
  • Autores: da Silva, I. V.; Mendez-Gimenez, L.; Camoes, S. P.; et al.
    Revista: FREE RADICAL BIOLOGY AND MEDICINE
    ISSN 0891-5849 Vol.120 N° Supl. 1 2018 págs. S61 - S62
  • Autores: Anon-Hidalgo, J.; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 69
  • Autores: Tuero Ojanguren, Carlota; Ahechu Garayoa, Patricia; Rotellar Sastre, Fernando; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 203
  • Autores: Escalada San Martín, Francisco Javier; Bonnet, F.; Wu, J. ; et al.
    Revista: VALUE IN HEALTH
    ISSN 1098-3015 Vol.21 N° Supl. 3 2018 págs. S120 - S120
  • Autores: Catalán Goñi, Victoria; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl. 1 2018 págs. 191
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN 0014-2972 Vol.48 N° Supl 1 2018 págs. 190 - 191
  • Autores: Morer Camo, María Paz; Paredes Puente, Jacobo; Llorente Ortega, Marcos; et al.
    Libro: Advances in Design Engineering II. INGEGRAF 2021
    ISSN 978-3-030-92426-3 2021 págs. 182 - 190
    Resumen
    The objective of this work has been the realization of a training simulator for neurosurgery operations using additive manufacturing. This work has been developed in collaboration with two neurosurgeons. The simulator developed contains two parts, a superficial skull inside which is the brain. Between both is the Dura Mater: a layer that cover the brain. The Dura Mater is a fibrous, solid, thick and not very flexible tissue, with a thickness of about 0.5 mm. In any brain operation, after having performed the craniotomy, the Dura Mater must be sutured. This membrane has a special consistency and the suture has to be made very close to the bone. Therefore, this complex skill must be trained. The Dura Mater must be replaced for each of the practices and satisfy with the thickness and consistency of human tissue so that it responds in a similar way to a suture performed in the operating room.
  • Autores: Silva Frojan, Camilo; García González, Javier Nicolás
    Libro: Balcells. La Clínica y el Laboratorio
    ISSN 978-84-9113-301-8 2019 págs. 761 - 780
  • Autores: Fernández González, Secundino
    Libro: Evaluación del paciente con disfonía
    ISSN 978-84-7867-593-7 2018 págs. 94 - 105

Proyectos desde 2018

  • Título: Utilidad clínica de GDF15 y FGF21 como biomarcadores de riesgo de diabetes tipo 2. Efecto del envejecimiento.
    Código de expediente: 58/2021
    Investigador principal: JAVIER GOMEZ AMBROSI.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2021 GN Proyectos de Investigación en salud
    Fecha de inicio: 23-12-2021
    Fecha fin: 22-12-2024
    Importe concedido: 79.925,00 €
    Fondos FEDER: SI
  • Título: Papel del inflamasoma en la regulación de la alteración de la barrera intestinal y la inflamación metabólica en un contexto de obesidad y diabetes tipo 2.
    Código de expediente: PI20/00927
    Investigador principal: VICTORIA CATALAN GOÑI.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2023
    Importe concedido: 156.695,00 €
    Fondos FEDER: SI
  • Título: Papel de GDF15 en las alteraciones metabólicas relacionadas con la edad en el contexto de la obesidad.
    Código de expediente: PI20/00080
    Investigador principal: JAVIER GOMEZ AMBROSI.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2023
    Importe concedido: 145.200,00 €
    Fondos FEDER: SI
  • Título: Papel de las adipo¿mioquinas en la susceptibilidad al desarrollo de COVID¿19 en la obesidad y diabetes tipo 2
    Código de expediente: 0011-3638-2020-000002
    Investigador principal: AMAIA RODRIGUEZ MURUETA-GOYENA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2020 GN Proyectos de Investigación en salud
    Fecha de inicio: 21-12-2020
    Fecha fin: 20-12-2021
    Importe concedido: 34.999,10 €
    Fondos FEDER: NO
  • Título: INNOLFACT: Implementación de Medicina de Precisión Olfatoria y Desarrollo de terapias nasales
    Código de expediente: 0011-1411-2020-000036
    Investigador principal: MARIA CRUZ RODRIGUEZ OROZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN PROYECTOS ESTRATEGICOS DE I+D 2020-2022
    Fecha de inicio: 01-07-2020
    Fecha fin: 30-11-2022
    Importe concedido: 601.228,00 €
    Fondos FEDER: NO
  • Título: Implicación de neogenina 1 en la inflamación del tejido adiposo asociada a la obesidad y sus comorbilidades.
    Código de expediente: PI19/00785
    Investigador principal: GEMA FRUHBECK MARTINEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 284.652,50 €
    Fondos FEDER: SI
  • Título: Implicación de guanilina y uroguanilina en el desarrollo de obesidad y resistencia a la insulina.
    Código de expediente: PI19/00990
    Investigador principal: AMAIA RODRIGUEZ MURUETA-GOYENA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 171.820,00 €
    Fondos FEDER: SI
  • Título: Papel del inflamasoma en la regulación de la inflamación, piroptosis y remodelado de la matriz extracelular en el desarrollo de cáncer de colon asociado a la obesidad.
    Código de expediente: 10/2018
    Investigador principal: VICTORIA CATALAN GOÑI.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2018 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2019
    Fecha fin: 31-12-2021
    Importe concedido: 79.350,00 €
    Fondos FEDER: SI
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia cardiaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra) (MINERVA)
    Código de expediente: 0011-1411-2018-000036
    Investigador principal: JUAN JOSE GAVIRA GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 97.237,60 €
    Fondos FEDER: NO
  • Título: Papel del inflamasoma en la regulación del inmunometabolismo, estrés oxidativo y remodelado de la matriz en la expansión del tejido adiposo asociada a la obesidad y sus comorbilidades.
    Código de expediente: PI17/02188
    Investigador principal: VICTORIA CATALAN GOÑI.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2017 PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 110.715,00 €
    Fondos FEDER: SI
  • Título: Papel de IL-1ß e IL-1RN en el desarrollo de alteraciones metabólicas mediadas por osteopontina en el contexto de la obesidad.
    Código de expediente: PI17/02183
    Investigador principal: JAVIER GOMEZ AMBROSI.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2017 PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 159.720,00 €
    Fondos FEDER: SI
  • Título: Desarrollo de una ecuación (CUN-BAE2) para estimar el porcentaje de grasa corporal de adultos a partir del índice de masa corporal, la edad, el género y la actividad física.
    Código de expediente: DTS17/00174
    Investigador principal: GEMA FRUHBECK MARTINEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES 2017 DESARROLLO TECNOLÓGICO EN SALUD
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2019
    Importe concedido: 33.550,00 €
    Fondos FEDER: SI
  • Título: Cambios en la plasticidad del tejido adiposo tras cirugía bariátrica y su papel en la mejoría de comorbilidades asociadas.
    Código de expediente: PI16/01217
    Investigador principal: GEMA FRUHBECK MARTINEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 260.452,50 €
    Fondos FEDER: SI
  • Título: Estudio de la interacción de adipoquinas y mioquinas en el desarrollo de obesidad y comorbilidades asociadas.
    Código de expediente: PI16/00221
    Investigador principal: AMAIA RODRIGUEZ MURUETA-GOYENA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 92.565,00 €
    Fondos FEDER: SI
  • Título: Estudio clínico y experimental del papel de la MMP-10 en la nefropatía diabética tipo 2
    Código de expediente: PI15/02111
    Investigador principal: NURIA GARCIA FERNANDEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2015 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2016
    Fecha fin: 30-11-2020
    Importe concedido: 116.765,00 €
    Fondos FEDER: SI